Variant 17-69129699-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080284.3(ABCA6):c.844G>A(p.Val282Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,600,192 control chromosomes in the GnomAD database, including 371,833 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.61 ( 29670 hom., cov: 31)

Exomes 𝑓: 0.68 ( 342163 hom. )

Consequence

ABCA6
NM_080284.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

ABCA6 (HGNC:36): (ATP binding cassette subfamily A member 6) The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This gene is clustered among 4 other ABC1 family members on 17q24 and may play a role in macrophage lipid homeostasis. [provided by RefSeq, Jul 2008]

ABCA6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.30586E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA6	NM_080284.3 linkuse as main transcript	c.844G>A	p.Val282Ile	missense_variant	7/39	ENST00000284425.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA6	ENST00000284425.7 linkuse as main transcript	c.844G>A	p.Val282Ile	missense_variant	7/39	1	NM_080284.3	P1	Q8N139-1

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92419

AN:

151704

Hom.:

29668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.807

Gnomad AMR

AF:

0.711

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.665

Gnomad FIN

AF:

0.667

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.708

Gnomad OTH

AF:

0.634

GnomAD3 exomes

AF:

0.660

AC:

164549

AN:

249280

Hom.:

55622

AF XY:

0.665

AC XY:

89662

AN XY:

134904

show subpopulations

Gnomad AFR exome

AF:

0.398

Gnomad AMR exome

AF:

0.734

Gnomad ASJ exome

AF:

0.608

Gnomad EAS exome

AF:

0.459

Gnomad SAS exome

AF:

0.670

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.707

Gnomad OTH exome

AF:

0.687

GnomAD4 exome

AF:

0.684

AC:

990035

AN:

1448370

Hom.:

342163

Cov.:

AF XY:

0.684

AC XY:

493508

AN XY:

721052

show subpopulations

Gnomad4 AFR exome

AF:

0.390

Gnomad4 AMR exome

AF:

0.732

Gnomad4 ASJ exome

AF:

0.605

Gnomad4 EAS exome

AF:

0.444

Gnomad4 SAS exome

AF:

0.673

Gnomad4 FIN exome

AF:

0.670

Gnomad4 NFE exome

AF:

0.703

Gnomad4 OTH exome

AF:

0.668

GnomAD4 genome

AF:

0.609

AC:

92471

AN:

151822

Hom.:

29670

Cov.:

AF XY:

0.609

AC XY:

45183

AN XY:

74176

show subpopulations

Gnomad4 AFR

AF:

0.401

Gnomad4 AMR

AF:

0.711

Gnomad4 ASJ

AF:

0.606

Gnomad4 EAS

AF:

0.452

Gnomad4 SAS

AF:

0.665

Gnomad4 FIN

AF:

0.667

Gnomad4 NFE

AF:

0.708

Gnomad4 OTH

AF:

0.635

Alfa

AF:

0.681

Hom.:

86163

Bravo

AF:

0.598

TwinsUK

AF:

0.709

AC:

2630

ALSPAC

AF:

0.697

AC:

2688

ESP6500AA

AF:

0.407

AC:

1793

ESP6500EA

AF:

0.698

AC:

5993

ExAC

AF:

0.655

AC:

79544

Asia WGS

AF:

0.565

AC:

1961

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.3

DANN

Benign

0.75

DEOGEN2

Benign

0.11

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0000033

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-2.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.53

REVEL

Benign

0.17

Sift

Benign

0.31

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.036

MPC

0.031

ClinPred

0.0069

GERP RS

2.1

Varity_R

0.021

gMVP

0.045

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over