NM_001378454.1(ALMS1):c.11953A>G (p.Ile3985Val) AND not specified

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Oct 4, 2019
Review status:: criteria provided, conflicting classifications

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:: RCV001195324.10

Allele description [Variation Report for NM_001378454.1(ALMS1):c.11953A>G (p.Ile3985Val)]

NM_001378454.1(ALMS1):c.11953A>G (p.Ile3985Val)

Genes:

ALMS1:ALMS1 centrosome and basal body associated protein [Gene - OMIM - HGNC]
LOC126806252:BRD4-independent group 4 enhancer GRCh37_chr2:73828496-73829695 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.1

Genomic location:

Preferred name:

NM_001378454.1(ALMS1):c.11953A>G (p.Ile3985Val)

HGVS:

NC_000002.12:g.73601275A>G
NG_011690.1:g.220523A>G
NM_001378454.1:c.11953A>GMANE SELECT
NM_015120.4:c.11956A>G
NP_001365383.1:p.Ile3985Val
NP_055935.4:p.Ile3986Val
LRG_741t1:c.11956A>G
LRG_741:g.220523A>G
LRG_741p1:p.Ile3986Val
NC_000002.11:g.73828402A>G
NM_001378454.1:c.11953A>G

Protein change:

I3985V

Links:

dbSNP: rs201728850

NCBI 1000 Genomes Browser:

rs201728850

Molecular consequence:

NM_001378454.1:c.11953A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_015120.4:c.11956A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001365667	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Oct 4, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002066449	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 1, 2019)	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

SCV001365667

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely benign
(Oct 4, 2019)

germline

clinical testing

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

SCV002066449

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 1, 2019)

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV001365667.1

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

Description

The p.Ile3986Val variant in ALMS1 is classified as likely benign because it has been identified in 0.1% (59/35436) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org), and computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1_Supporting, BP4.

#	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		1	not provided	1	not provided

From Genetic Services Laboratory, University of Chicago, SCV002066449.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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