Variant 16-16221750-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001171.6(ABCC6):c.118C>T(p.Pro40Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,504 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 Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ABCC6
NM_001171.6 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 6.45

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABCC6	NM_001171.6 linkuse as main transcript	c.118C>T	p.Pro40Ser	missense_variant	2/31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001079528.4 linkuse as main transcript	c.118C>T	p.Pro40Ser	missense_variant	2/2		NP_001072996.1
ABCC6	NM_001351800.1 linkuse as main transcript	c.-256C>T		5_prime_UTR_variant	2/31		NP_001338729.1
ABCC6	NR_147784.1 linkuse as main transcript	n.155C>T		non_coding_transcript_exon_variant	2/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12 linkuse as main transcript	c.118C>T	p.Pro40Ser	missense_variant	2/31	1	NM_001171.6	ENSP00000205557	P1	O95255-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461504

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727048

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 provided

research

PXE International

Feb 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.56

D;.;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.82

T;T;.

M_CAP

Pathogenic

0.55

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Uncertain

-0.035

MutationAssessor

Pathogenic

3.3

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-6.2

D;.;.

REVEL

Pathogenic

0.83

Sift

Uncertain

0.0010

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.89

MutPred

0.77

Loss of catalytic residue at P40 (P = 0.1947);Loss of catalytic residue at P40 (P = 0.1947);Loss of catalytic residue at P40 (P = 0.1947);

MVP

0.82

MPC

2.4

ClinPred

1.0

GERP RS

4.4

Varity_R

0.61

gMVP

0.70

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.

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