NM_001171.6:c.1424A>T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate

The NM_001171.6(ABCC6):c.1424A>T(p.His475Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,613,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

ABCC6
NM_001171.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5B:1

Conservation

PhyloP100: 0.481

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 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

BP4

Computational evidence support a benign effect (MetaRNN=0.1215654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ABCC6	NM_001171.6 link	c.1424A>T	p.His475Leu	missense_variant	Exon 11 of 31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 link	c.1082A>T	p.His361Leu	missense_variant	Exon 11 of 31		NP_001338729.1
ABCC6	NR_147784.1 link	n.1461A>T		non_coding_transcript_exon_variant	Exon 11 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCC6	ENST00000205557.12 link	c.1424A>T	p.His475Leu	missense_variant	Exon 11 of 31	1	NM_001171.6	ENSP00000205557.7	O95255-1
ABCC6	ENST00000456970.6 link	n.1424A>T		non_coding_transcript_exon_variant	Exon 11 of 29	2		ENSP00000405002.2	O95255-3
ABCC6	ENST00000622290.5 link	n.1424A>T		non_coding_transcript_exon_variant	Exon 11 of 32	5		ENSP00000483331.2	A0A8C8Q0G8

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000255

AC:

AN:

251146

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000579

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:

0.000485

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000296

AC:

432

AN:

1461654

Hom.:

Cov.:

AF XY:

0.000292

AC XY:

212

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000112

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:

0.000370

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000224

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000454

Hom.:

Bravo

AF:

0.000246

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000255

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.000652

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:5Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 01, 2017

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 02, 2016

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive inherited pseudoxanthoma elasticum

Uncertain:1

Aug 17, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal dystrophy

Uncertain:1

Jan 01, 2022

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2

Uncertain:1

Oct 31, 2018

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

0.083

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.075

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.55

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.3

N;.

REVEL

Uncertain

0.49

Sift

Benign

0.41

T;.

Sift4G

Benign

0.28

T;T

Polyphen

0.12

B;.

Vest4

0.32

MVP

0.81

MPC

0.082

ClinPred

0.021

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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