rs74315110
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PM4PP5_Moderate
The NM_001171.6(ABCC6):c.179_187delGGGGCTACC(p.Arg60_Tyr62del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.000011 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ABCC6
NM_001171.6 disruptive_inframe_deletion
NM_001171.6 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.47
Publications
1 publications found
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]
ABCC6 Gene-Disease associations (from GenCC):
- arterial calcification, generalized, of infancy, 2Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
- autosomal recessive inherited pseudoxanthoma elasticumInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P
- arterial calcification of infancyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001171.6.
PP5
Variant 16-16221680-AGGTAGCCCC-A is Pathogenic according to our data. Variant chr16-16221680-AGGTAGCCCC-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 433371.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001171.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ABCC6 | NM_001171.6 | MANE Select | c.179_187delGGGGCTACC | p.Arg60_Tyr62del | disruptive_inframe_deletion | Exon 2 of 31 | NP_001162.5 | ||
| ABCC6 | NM_001440309.1 | c.179_187delGGGGCTACC | p.Arg60_Tyr62del | disruptive_inframe_deletion | Exon 2 of 31 | NP_001427238.1 | |||
| ABCC6 | NM_001440310.1 | c.179_187delGGGGCTACC | p.Arg60_Tyr62del | disruptive_inframe_deletion | Exon 2 of 30 | NP_001427239.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ABCC6 | ENST00000205557.12 | TSL:1 MANE Select | c.179_187delGGGGCTACC | p.Arg60_Tyr62del | disruptive_inframe_deletion | Exon 2 of 31 | ENSP00000205557.7 | ||
| ABCC6 | ENST00000575728.1 | TSL:1 | c.179_187delGGGGCTACC | p.Arg60_Tyr62del | disruptive_inframe_deletion | Exon 2 of 2 | ENSP00000461686.1 | ||
| ABCC6 | ENST00000574094.6 | TSL:5 | c.179_187delGGGGCTACC | p.Arg60_Tyr62del | disruptive_inframe_deletion | Exon 2 of 11 | ENSP00000507301.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000109 AC: 16AN: 1461656Hom.: 0 AF XY: 0.0000138 AC XY: 10AN XY: 727138 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
16
AN:
1461656
Hom.:
AF XY:
AC XY:
10
AN XY:
727138
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86244
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
16
AN:
1111836
Other (OTH)
AF:
AC:
0
AN:
60378
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000242251), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.391
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
30
ClinVar
ClinVar submissions as Germline
Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Autosomal recessive inherited pseudoxanthoma elasticum (1)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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