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rs957828732

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001171.6(ABCC6):c.268G>A(p.Ala90Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 24)
Exomes 𝑓: 0.000012 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ABCC6
NM_001171.6 missense

Scores

19

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -0.577
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.08822027).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCC6NM_001171.6 linkuse as main transcriptc.268G>A p.Ala90Thr missense_variant 3/31 ENST00000205557.12
ABCC6NM_001351800.1 linkuse as main transcriptc.-75G>A 5_prime_UTR_variant 3/31
ABCC6NR_147784.1 linkuse as main transcriptn.305G>A non_coding_transcript_exon_variant 3/29

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCC6ENST00000205557.12 linkuse as main transcriptc.268G>A p.Ala90Thr missense_variant 3/311 NM_001171.6 P1O95255-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
3
AN:
151658
Hom.:
0
Cov.:
24
FAILED QC
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000116
AC:
15
AN:
1292292
Hom.:
0
Cov.:
21
AF XY:
0.0000109
AC XY:
7
AN XY:
643040
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000129
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000132
Gnomad4 OTH exome
AF:
0.0000184
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000198
AC:
3
AN:
151658
Hom.:
0
Cov.:
24
AF XY:
0.0000270
AC XY:
2
AN XY:
74036
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Uncertain:1
Uncertain significance, no assertion criteria providedresearchPXE InternationalFeb 02, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.69
Cadd
Benign
12
Dann
Benign
0.81
DEOGEN2
Benign
0.11
T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0050
N
LIST_S2
Benign
0.53
T;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.088
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-0.33
N;N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.070
N;.
REVEL
Benign
0.019
Sift
Benign
0.26
T;.
Sift4G
Benign
0.72
T;T
Polyphen
0.0
B;.
Vest4
0.12
MutPred
0.46
Loss of helix (P = 0.028);Loss of helix (P = 0.028);
MVP
0.18
MPC
1.2
ClinPred
0.015
T
GERP RS
-3.0
Varity_R
0.049
gMVP
0.084

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs957828732; hg19: chr16-16313756; API