rs72657694
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_001171.6(ABCC6):c.3168C>T(p.Asp1056=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000083 ( 0 hom. )
Consequence
ABCC6
NM_001171.6 synonymous
NM_001171.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.724
Genes affected
ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) 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). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 16-16165761-G-A is Benign according to our data. Variant chr16-16165761-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1297675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16165761-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.724 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.3168C>T | p.Asp1056= | synonymous_variant | 23/31 | ENST00000205557.12 | |
ABCC6 | NM_001351800.1 | c.2826C>T | p.Asp942= | synonymous_variant | 23/31 | ||
ABCC6 | NR_147784.1 | n.3030C>T | non_coding_transcript_exon_variant | 22/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.3168C>T | p.Asp1056= | synonymous_variant | 23/31 | 1 | NM_001171.6 | P1 | |
ABCC6 | ENST00000622290.5 | c.3168C>T | p.Asp1056= | synonymous_variant, NMD_transcript_variant | 23/32 | 5 | |||
ABCC6 | ENST00000456970.6 | c.*377C>T | 3_prime_UTR_variant, NMD_transcript_variant | 22/29 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152216Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000111 AC: 28AN: 251242Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135896
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GnomAD4 exome AF: 0.0000828 AC: 121AN: 1461450Hom.: 0 Cov.: 33 AF XY: 0.0000839 AC XY: 61AN XY: 727008
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
ABCC6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 09, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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