17-69129699-C-T

Position:

• chr17-69129699-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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]

ACMG classification

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	Protein	UniProt
ABCA6	NM_080284.3	c.844G>A	p.Val282Ile	missense_variant	7/39	ENST00000284425.7	NP_525023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA6	ENST00000284425.7	c.844G>A	p.Val282Ile	missense_variant	7/39	1	NM_080284.3	ENSP00000284425	P1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92419 AN: 151704 Hom.: 29668 Cov.: 31

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

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.: 31 AF XY: 0.684 AC XY: 493508 AN XY: 721052

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.: 31 AF XY: 0.609 AC XY: 45183 AN XY: 74176

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	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.3
DANN	Benign	0.75
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0000033	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-2.1	N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.17
Sift	Benign	0.31	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.036
MPC		0.031
ClinPred		0.0069	T
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

Other links and lift over

dbSNP: rs4968839; hg19: chr17-67125840; COSMIC: COSV52636800;