Variant chr17-69085046-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080284.3(ABCA6):c.4166C>A(p.Ala1389Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,398 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ABCA6
NM_080284.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.754

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA6	NM_080284.3 linkuse as main transcript	c.4166C>A	p.Ala1389Glu	missense_variant	32/39	ENST00000284425.7	NP_525023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA6	ENST00000284425.7 linkuse as main transcript	c.4166C>A	p.Ala1389Glu	missense_variant	32/39	1	NM_080284.3	ENSP00000284425	P1	Q8N139-1
ABCA6	ENST00000446604.6 linkuse as main transcript	n.1432C>A		non_coding_transcript_exon_variant	11/18	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458398

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000231

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

The c.4166C>A (p.A1389E) alteration is located in exon 32 (coding exon 31) of the ABCA6 gene. This alteration results from a C to A substitution at nucleotide position 4166, causing the alanine (A) at amino acid position 1389 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

Eigen

Benign

0.10

Eigen_PC

Benign

-0.083

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.84

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.74

MetaSVM

Pathogenic

0.88

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.44

Sift

Uncertain

0.012

Sift4G

Uncertain

0.049

Polyphen

0.98

Vest4

0.47

MutPred

0.68

Loss of MoRF binding (P = 0.0517);

MVP

0.90

MPC

0.25

ClinPred

0.84

GERP RS

4.8

Varity_R

0.68

gMVP

0.59

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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