rs8058694

Positions:

chr16-16185006-G-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001171.6(ABCC6):c.1896C>A(p.His632Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,608,938 control chromosomes in the GnomAD database, including 178,917 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14343 hom., cov: 31)

Exomes 𝑓: 0.47 ( 164574 hom. )

Consequence

ABCC6
NM_001171.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a domain ABC transporter 1 (size 224) in uniprot entity MRP6_HUMAN there are 31 pathogenic changes around while only 5 benign (86%) in NM_001171.6

BP4

Computational evidence support a benign effect (MetaRNN=2.1311641E-4).

BP6

Variant 16-16185006-G-T is Benign according to our data. Variant chr16-16185006-G-T is described in ClinVar as [Benign]. Clinvar id is 433247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16185006-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABCC6	NM_001171.6 linkuse as main transcript	c.1896C>A	p.His632Gln	missense_variant	15/31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 linkuse as main transcript	c.1554C>A	p.His518Gln	missense_variant	15/31		NP_001338729.1
ABCC6	NR_147784.1 linkuse as main transcript	n.1933C>A		non_coding_transcript_exon_variant	15/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCC6	ENST00000205557.12 linkuse as main transcript	c.1896C>A	p.His632Gln	missense_variant	15/31	1	NM_001171.6	ENSP00000205557.7	O95255-1
ABCC6	ENST00000456970.6 linkuse as main transcript	n.1896C>A		non_coding_transcript_exon_variant	15/29	2		ENSP00000405002.2	O95255-3
ABCC6	ENST00000622290.5 linkuse as main transcript	n.1896C>A		non_coding_transcript_exon_variant	15/32	5		ENSP00000483331.2	A0A8C8Q0G8

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64716

AN:

151590

Hom.:

14342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.516

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.425

GnomAD3 exomes

AF:

0.419

AC:

105156

AN:

251100

Hom.:

23455

AF XY:

0.413

AC XY:

56008

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.159

Gnomad SAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.445

GnomAD4 exome

AF:

0.468

AC:

681571

AN:

1457230

Hom.:

164574

Cov.:

AF XY:

0.461

AC XY:

334447

AN XY:

725092

show subpopulations

Gnomad4 AFR exome

AF:

0.349

Gnomad4 AMR exome

AF:

0.468

Gnomad4 ASJ exome

AF:

0.428

Gnomad4 EAS exome

AF:

0.186

Gnomad4 SAS exome

AF:

0.261

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.501

Gnomad4 OTH exome

AF:

0.437

GnomAD4 genome

AF:

0.427

AC:

64726

AN:

151708

Hom.:

14343

Cov.:

AF XY:

0.417

AC XY:

30888

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.354

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.499

Gnomad4 OTH

AF:

0.419

Alfa

AF:

0.464

Hom.:

22533

Bravo

AF:

0.428

TwinsUK

AF:

0.495

AC:

1836

ALSPAC

AF:

0.492

AC:

1895

ESP6500AA

AF:

0.358

AC:

1574

ESP6500EA

AF:

0.502

AC:

4313

ExAC

AF:

0.415

AC:

50419

Asia WGS

AF:

0.211

AC:

731

AN:

3478

EpiCase

AF:

0.483

EpiControl

AF:

0.479

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Autosomal recessive inherited pseudoxanthoma elasticum

Benign:2

Benign, criteria provided, single submitter	research	PXE International	Mar 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Pseudoxanthoma elasticum, forme fruste

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Arterial calcification, generalized, of infancy, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.051

DANN

Benign

0.61

DEOGEN2

Benign

0.097

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.27

T;T

MetaRNN

Benign

0.00021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.62

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.72

N;.

REVEL

Uncertain

0.29

Sift

Benign

0.24

T;.

Sift4G

Benign

0.65

T;T

Polyphen

0.0010

B;.

Vest4

0.026

MutPred

0.29

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MPC

0.067

ClinPred

1.0

GERP RS

-9.0

Varity_R

0.14

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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