Variant chr16-16203457-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM5PP3_StrongPP5

The NM_001171.6(ABCC6):c.951C>A(p.Ser317Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S317?) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ABCC6
NM_001171.6 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.73

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]

ABCC6 links:

ABCC6 (HGNC:):

ABCC6 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1

In a domain ABC transmembrane type-1 1 (size 282) in uniprot entity MRP6_HUMAN there are 31 pathogenic changes around while only 9 benign (78%) in NM_001171.6

PM5

Other missense variant is known to change same aminoacid residue: Variant chr16-16203457-G-Y is described in Lovd as [Pathogenic].

PP3

MetaRNN computational evidence supports a deleterious effect, 0.973

PP5

Variant 16-16203457-G-T is Pathogenic according to our data. Variant chr16-16203457-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 433366.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABCC6	NM_001171.6 linkuse as main transcript	c.951C>A	p.Ser317Arg	missense_variant	8/31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 linkuse as main transcript	c.609C>A	p.Ser203Arg	missense_variant	8/31		NP_001338729.1
ABCC6	NR_147784.1 linkuse as main transcript	n.988C>A		non_coding_transcript_exon_variant	8/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12 linkuse as main transcript	c.951C>A	p.Ser317Arg	missense_variant	8/31	1	NM_001171.6	ENSP00000205557.7		O95255-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251136

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135724

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:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727144

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000279

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum

Pathogenic:1

Pathogenic, no assertion criteria provided

research

PXE International

Mar 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.86

D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Uncertain

0.23

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.2

N;.

REVEL

Pathogenic

0.76

Sift

Benign

0.084

T;.

Sift4G

Benign

0.11

T;D

Polyphen

0.95

P;.

Vest4

0.85

MutPred

0.93

Gain of methylation at S317 (P = 0.0168);Gain of methylation at S317 (P = 0.0168);

MVP

0.88

MPC

0.17

ClinPred

0.38

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.72

gMVP

0.75

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over