Menu
GeneBe

rs72653800

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001171.6(ABCC6):c.2643G>T(p.Arg881Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ABCC6
NM_001171.6 missense

Scores

2
11

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.0350
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 -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.37552774).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCC6NM_001171.6 linkuse as main transcriptc.2643G>T p.Arg881Ser missense_variant 20/31 ENST00000205557.12
ABCC6NM_001351800.1 linkuse as main transcriptc.2301G>T p.Arg767Ser missense_variant 20/31
ABCC6NR_147784.1 linkuse as main transcriptn.2505G>T non_coding_transcript_exon_variant 19/29

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCC6ENST00000205557.12 linkuse as main transcriptc.2643G>T p.Arg881Ser missense_variant 20/311 NM_001171.6 P1O95255-1
ABCC6ENST00000576683.1 linkuse as main transcriptn.130G>T non_coding_transcript_exon_variant 2/33
ABCC6ENST00000622290.5 linkuse as main transcriptc.2643G>T p.Arg881Ser missense_variant, NMD_transcript_variant 20/325
ABCC6ENST00000456970.6 linkuse as main transcriptc.2468G>T p.Gly823Val missense_variant, NMD_transcript_variant 19/292 O95255-3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251168
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461866
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
727228
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
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
0.10
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Uncertain
-0.080
Cadd
Benign
3.5
Dann
Benign
0.48
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.079
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.77
T
MutationTaster
Benign
1.0
N
Sift4G
Uncertain
0.022
D
Vest4
0.41
MutPred
0.76
Loss of catalytic residue at P819 (P = 0.0722);
MVP
0.092
ClinPred
0.026
T
GERP RS
-0.64
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs72653800; hg19: chr16-16269791; API