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NM_000443.4(ABCB4):c.959C>T (p.Ser320Phe) AND Progressive familial intrahepatic cholestasis type 3

Germline classification:
no classifications from unflagged records (1 submission)
Last evaluated:
Jul 24, 2023
Review status:
no classifications from unflagged records
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:
RCV000190560.7

Allele description [Variation Report for NM_000443.4(ABCB4):c.959C>T (p.Ser320Phe)]

NM_000443.4(ABCB4):c.959C>T (p.Ser320Phe)

Gene:
ABCB4:ATP binding cassette subfamily B member 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q21.12
Genomic location:
Preferred name:
NM_000443.4(ABCB4):c.959C>T (p.Ser320Phe)
HGVS:
  • NC_000007.14:g.87447080G>A
  • NG_007118.2:g.38353C>T
  • NM_000443.4:c.959C>TMANE SELECT
  • NM_018849.3:c.959C>T
  • NM_018850.3:c.959C>T
  • NP_000434.1:p.Ser320Phe
  • NP_061337.1:p.Ser320Phe
  • NP_061338.1:p.Ser320Phe
  • NC_000007.13:g.87076396G>A
  • NM_000443.3:c.959C>T
  • NM_018849.2:c.959C>T
  • P21439:p.Ser320Phe
Protein change:
S320F; SER320PHE
Links:
UniProtKB: P21439#VAR_023502; OMIM: 171060.0005; dbSNP: rs72552778
NCBI 1000 Genomes Browser:
rs72552778
Molecular consequence:
  • NM_000443.4:c.959C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018849.3:c.959C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018850.3:c.959C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Progressive familial intrahepatic cholestasis type 3
Synonyms:
Progressive familial intrahepatic cholestasis with elevated serum gamma-glutamyltransferase; MDR3 deficiency; Low Gamma-GT Familial Intrahepatic Cholestasis
Identifiers:
MONDO: MONDO:0011214; MedGen: C1865643; Orphanet: 79305; OMIM: 602347

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Assertion and evidence details

Help
No clinical assertions found. See "Flagged submissions" below.
Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3).

Degiorgio D, Colombo C, Seia M, Porcaro L, Costantino L, Zazzeron L, Bordo D, Coviello DA.

Eur J Hum Genet. 2007 Dec;15(12):1230-8. Epub 2007 Aug 29.

PubMed [citation]
PMID:
17726488

Combined functional variants of hepatobiliary transporters and FXR aggravate intrahepatic cholestasis of pregnancy.

Zimmer V, Müllenbach R, Simon E, Bartz C, Matern S, Lammert F.

Liver Int. 2009 Sep;29(8):1286-8. doi: 10.1111/j.1478-3231.2009.02026.x. No abstract available.

PubMed [citation]
PMID:
19490418
See all PubMed Citations (12)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq, SCV000245567.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (12)

Description

The Ser320Phe variant in ABCB4 has been reported in 9 heterozygous, 6 homozygous, and 4 compound heterozygous individuals with cholestatic liver disease (Andress 2014, Poupon 2013, Wendum 2012, Bacq 2009, Degiorgio 2007, Colombo 2011, Rosmorduc 2001, Pauli-Magnus 2004, Zimmer 2009, Keitel 2006). This variant has been identified in 1/8600 of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs72552778). Computational analyses (biochemical amino acid properties, conservation and PolyPhen2) do not provide strong support for or against an impact to the protein. In vitro assays suggest the Ser320Phe variant may affect protein function (Andress 2014, Kim 2013); however these types of assays may not accurately represent biological function. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the Ser320Phe variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Flagged submissions

Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000245567Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq
flagged submission
Reason: Outlier claim with insufficient supporting evidence
Notes: None

(LMM Criteria)		Uncertain significance
(Aug 22, 2014) 		germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

Last Updated: Oct 26, 2024