rs1555523855

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001171.6(ABCC6):​c.26C>A​(p.Ala9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ABCC6
NM_001171.6 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.133
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17422995).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCC6NM_001171.6 linkc.26C>A p.Ala9Glu missense_variant Exon 1 of 31 ENST00000205557.12 NP_001162.5
ABCC6NM_001079528.4 linkc.26C>A p.Ala9Glu missense_variant Exon 1 of 2 NP_001072996.1
ABCC6NM_001351800.1 linkc.-348C>A 5_prime_UTR_variant Exon 1 of 31 NP_001338729.1
ABCC6NR_147784.1 linkn.63C>A non_coding_transcript_exon_variant Exon 1 of 29

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCC6ENST00000205557.12 linkc.26C>A p.Ala9Glu missense_variant Exon 1 of 31 1 NM_001171.6 ENSP00000205557.7 O95255-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1293828
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
634798
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Uncertain:1
Feb 02, 2021
PXE International
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: research

- -

Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2 Uncertain:1
May 31, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
9.8
DANN
Benign
0.95
DEOGEN2
Benign
0.15
T;.;.
Eigen
Benign
-0.90
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.62
T;T;.
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.49
N;N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.94
N;.;.
REVEL
Benign
0.054
Sift
Benign
0.033
D;.;.
Sift4G
Uncertain
0.031
D;D;D
Polyphen
0.11
B;.;.
Vest4
0.092
MutPred
0.72
Gain of disorder (P = 0.0209);Gain of disorder (P = 0.0209);Gain of disorder (P = 0.0209);
MVP
0.51
MPC
1.5
ClinPred
0.37
T
GERP RS
-0.43
Varity_R
0.12
gMVP
0.28

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: rs1555523855; hg19: chr16-16317266; API