Variant 17-69152059-C-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_001377321.1(ABCA10):c.4381G>A(p.Ala1461Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ABCA10
NM_001377321.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

Variant links:

Genes affected

ABCA10 (HGNC:30): (ATP binding cassette subfamily A member 10) 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, but neither the substrate nor the function of this gene is known. [provided by RefSeq, Jul 2008]

ABCA10 links:

ABCA10 (HGNC:):

ABCA10 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
ABCA10	NM_001377321.1 linkuse as main transcript	c.4381G>A	p.Ala1461Thr	missense_variant	36/39	ENST00000690296.1	NP_001364250.1
ABCA10	NM_080282.4 linkuse as main transcript	c.4381G>A	p.Ala1461Thr	missense_variant	37/40		NP_525021.3	Q8WWZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCA10	ENST00000690296.1 linkuse as main transcript	c.4381G>A	p.Ala1461Thr	missense_variant	36/39		NM_001377321.1	ENSP00000509702.1	Q8WWZ4-1
ABCA10	ENST00000522406.5 linkuse as main transcript	n.*3309G>A		non_coding_transcript_exon_variant	38/41	1		ENSP00000429853.1	Q8WWZ4-5
ABCA10	ENST00000522406.5 linkuse as main transcript	n.*3309G>A		3_prime_UTR_variant	38/41	1		ENSP00000429853.1	Q8WWZ4-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

247858

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000339

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.86e-7

AC:

AN:

1458030

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Feb 06, 2024

The c.4381G>A (p.A1461T) alteration is located in exon 37 (coding exon 34) of the ABCA10 gene. This alteration results from a G to A substitution at nucleotide position 4381, causing the alanine (A) at amino acid position 1461 to be replaced by a threonine (T). 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

0.30

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

0.50

MutationAssessor

Pathogenic

3.1

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.55

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.56

MutPred

0.38

Gain of ubiquitination at K1456 (P = 0.1008);

MVP

0.83

MPC

0.22

ClinPred

0.97

GERP RS

2.1

Varity_R

0.33

gMVP

0.13

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

Other links and lift over