chr16-48175364-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001370497.1(ABCC11):c.3592C>T(p.Arg1198Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )
Consequence
ABCC11
NM_001370497.1 missense
NM_001370497.1 missense
Scores
2
8
8
Clinical Significance
Conservation
PhyloP100: 1.06
Genes affected
ABCC11 (HGNC:14639): (ATP binding cassette subfamily C member 11) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This ABC full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a SNP in this gene is responsible for determination of human earwax type. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC11 | NM_001370497.1 | c.3592C>T | p.Arg1198Trp | missense_variant | 26/30 | ENST00000356608.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC11 | ENST00000356608.7 | c.3592C>T | p.Arg1198Trp | missense_variant | 26/30 | 1 | NM_001370497.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251166Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135800
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GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461706Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 727108
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74374
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2022 | The c.3592C>T (p.R1198W) alteration is located in exon 26 (coding exon 25) of the ABCC11 gene. This alteration results from a C to T substitution at nucleotide position 3592, causing the arginine (R) at amino acid position 1198 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Pathogenic
D;.;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M;M;M
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
B;D;D;D
Vest4
MVP
MPC
0.49
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at