NM_175914.5(HNF4A):c.358T>C (p.Ser120Pro) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 9, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000992164.7

Allele description [Variation Report for NM_175914.5(HNF4A):c.358T>C (p.Ser120Pro)]

NM_175914.5(HNF4A):c.358T>C (p.Ser120Pro)

Gene:

HNF4A:hepatocyte nuclear factor 4 alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_175914.5(HNF4A):c.358T>C (p.Ser120Pro)

HGVS:

NC_000020.11:g.44413732T>C
NG_009818.1:g.62932T>C
NM_000457.6:c.424T>C
NM_001030003.3:c.358T>C
NM_001030004.3:c.358T>C
NM_001258355.2:c.403T>C
NM_001287182.2:c.349T>C
NM_001287183.2:c.349T>C
NM_001287184.2:c.349T>C
NM_175914.5:c.358T>CMANE SELECT
NM_178849.3:c.424T>C
NM_178850.3:c.424T>C
NP_000448.3:p.Ser142Pro
NP_000448.3:p.Ser142Pro
NP_001025174.1:p.Ser120Pro
NP_001025175.1:p.Ser120Pro
NP_001245284.1:p.Ser135Pro
NP_001274111.1:p.Ser117Pro
NP_001274112.1:p.Ser117Pro
NP_001274113.1:p.Ser117Pro
NP_787110.2:p.Ser120Pro
NP_849180.1:p.Ser142Pro
NP_849181.1:p.Ser142Pro
LRG_483t1:c.358T>C
LRG_483t2:c.424T>C
LRG_483:g.62932T>C
LRG_483p2:p.Ser142Pro
NC_000020.10:g.43042372T>C
NC_000020.10:g.43042372T>C
NM_000457.4:c.424T>C
NM_175914.4:c.358T>C

Protein change:

S117P

Links:

dbSNP: rs780342162

NCBI 1000 Genomes Browser:

rs780342162

Molecular consequence:

NM_000457.6:c.424T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001030003.3:c.358T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001030004.3:c.358T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001258355.2:c.403T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001287182.2:c.349T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001287183.2:c.349T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001287184.2:c.349T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_175914.5:c.358T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_178849.3:c.424T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_178850.3:c.424T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens proteasome (prosome, macropain) subunit, alpha type, 2 (PSMA2), mRN...
Homo sapiens proteasome (prosome, macropain) subunit, alpha type, 2 (PSMA2), mRNA
gi|4506180|ref|NM_002787.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001144209	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Feb 13, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003021994	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 9, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001144209

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Feb 13, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003021994

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 9, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Athena Diagnostics, SCV001144209.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003021994.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 120 of the HNF4A protein (p.Ser120Pro). This variant is present in population databases (rs780342162, gnomAD 0.03%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on HNF4A protein function. ClinVar contains an entry for this variant (Variation ID: 804915). This variant has not been reported in the literature in individuals affected with HNF4A-related conditions.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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