rs72657689

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_001171.6(ABCC6):c.2848G>A(p.Ala950Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000301 in 1,579,638 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A950V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

ABCC6
NM_001171.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:6

Conservation

PhyloP100: 0.456

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

arterial calcification, generalized, of infancy, 2
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
autosomal recessive inherited pseudoxanthoma elasticum
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Orphanet
inherited pseudoxanthoma elasticum
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
arterial calcification of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ABCC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 16-16169793-C-T is Benign according to our data. Variant chr16-16169793-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 381637.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCC6	NM_001171.6	MANE Select	c.2848G>A	p.Ala950Thr	missense	Exon 22 of 31	NP_001162.5
ABCC6	NM_001440309.1		c.2815G>A	p.Ala939Thr	missense	Exon 22 of 31	NP_001427238.1
ABCC6	NM_001440310.1		c.2680G>A	p.Ala894Thr	missense	Exon 21 of 30	NP_001427239.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.2848G>A	p.Ala950Thr	missense	Exon 22 of 31	ENSP00000205557.7	O95255-1
ABCC6	ENST00000909083.1		c.2848G>A	p.Ala950Thr	missense	Exon 22 of 32	ENSP00000579142.1
ABCC6	ENST00000909090.1		c.2848G>A	p.Ala950Thr	missense	Exon 22 of 32	ENSP00000579149.1

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000551

AC:

104

AN:

188620

AF XY:

0.000562

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00957

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000138

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

AF:

0.000294

AC:

419

AN:

1427326

Hom.:

Cov.:

AF XY:

0.000320

AC XY:

226

AN XY:

706934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32684

American (AMR)

AF:

0.000180

AC:

AN:

38990

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

280

AN:

25480

East Asian (EAS)

AF:

0.0000264

AC:

AN:

37810

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50600

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.0000639

AC:

AN:

1095098

Other (OTH)

AF:

0.000998

AC:

AN:

59104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

108

144

180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000368

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41576

American (AMR)

AF:

0.0000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000623

Hom.:

Bravo

AF:

0.000382

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000293

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive inherited pseudoxanthoma elasticum (3)

not provided (3)

ABCC6-related disorder (1)

Arterial calcification, generalized, of infancy, 2 (1)

Pseudoxanthoma elasticum, forme fruste (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.16

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.63

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.44

MutationAssessor

Benign

-0.55

PhyloP100

0.46

PrimateAI

Benign

0.28

PROVEAN

Benign

0.65

REVEL

Uncertain

0.53

Sift

Benign

1.0

Sift4G

Benign

0.30

Polyphen

0.0070

Vest4

0.094

MVP

0.40

MPC

0.066

ClinPred

0.026

GERP RS

-2.3

Varity_R

0.049

gMVP

0.14

Mutation Taster

=34/66

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: -24

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over