17-69105577-C-T

Position:

• chr17-69105577-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.2625G>A​(p.Met875Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 1,559,994 control chromosomes in the GnomAD database, including 649,929 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.79 (50556 hom., cov: 31)
  • Exomes 𝑓: 0.92 (599373 hom.)
• Consequence: ABCA6 NM_080284.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.184725E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA6	NM_080284.3	c.2625G>A	p.Met875Ile	missense_variant	20/39	ENST00000284425.7	NP_525023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA6	ENST00000284425.7	c.2625G>A	p.Met875Ile	missense_variant	20/39	1	NM_080284.3	ENSP00000284425.1
ABCA6	ENST00000590311.5	n.6521G>A		non_coding_transcript_exon_variant	5/5	1
ABCA6	ENST00000589803.5	n.1620G>A		non_coding_transcript_exon_variant	9/9	5

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119742 AN: 151948 Hom.: 50561 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.830

GnomAD3 exomes AF: 0.878 AC: 217200 AN: 247348 Hom.: 97313 AF XY: 0.892 AC XY: 119212 AN XY: 133668

Gnomad AFR exome AF: 0.445

Gnomad AMR exome AF: 0.804

Gnomad ASJ exome AF: 0.930

Gnomad EAS exome AF: 0.852

Gnomad SAS exome AF: 0.916

Gnomad FIN exome AF: 0.912

Gnomad NFE exome AF: 0.944

Gnomad OTH exome AF: 0.899

GnomAD4 exome AF: 0.919 AC: 1293811 AN: 1407928 Hom.: 599373 Cov.: 31 AF XY: 0.921 AC XY: 647358 AN XY: 702662

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.803

Gnomad4 ASJ exome AF: 0.933

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.915

Gnomad4 FIN exome AF: 0.914

Gnomad4 NFE exome AF: 0.942

Gnomad4 OTH exome AF: 0.894

GnomAD4 genome AF: 0.788 AC: 119764 AN: 152066 Hom.: 50556 Cov.: 31 AF XY: 0.788 AC XY: 58575 AN XY: 74342

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.921

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.828

Alfa AF: 0.917 Hom.: 157865

Bravo AF: 0.761

TwinsUK AF: 0.941 AC: 3489

ALSPAC AF: 0.944 AC: 3638

ESP6500AA AF: 0.464 AC: 2044

ESP6500EA AF: 0.941 AC: 8090

ExAC AF: 0.876 AC: 106322

Asia WGS AF: 0.875 AC: 3036 AN: 3474

EpiCase AF: 0.943

EpiControl AF: 0.940

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.0060
DANN	Benign	0.51
DEOGEN2	Benign	0.088	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.55	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.13
Sift	Benign	0.47	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.015
MutPred		0.24		Gain of catalytic residue at M875 (P = 0.001);
MPC		0.037
ClinPred		0.00099	T
GERP RS		-1.7
Varity_R		0.031
gMVP		0.037

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: rs7212506; hg19: chr17-67101718;