chr17-69150063-T-A

Position:

chr17-69150063-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001377321.1(ABCA10):c.4398A>T(p.Arg1466Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,607,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ABCA10
NM_001377321.1 missense, splice_region

Scores

Splicing: ADA: 0.0006061

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.70

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05555752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA10	NM_001377321.1 linkuse as main transcript	c.4398A>T	p.Arg1466Ser	missense_variant, splice_region_variant	37/39	ENST00000690296.1	NP_001364250.1
ABCA10	NM_080282.4 linkuse as main transcript	c.4398A>T	p.Arg1466Ser	missense_variant, splice_region_variant	38/40		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.4398A>T	p.Arg1466Ser	missense_variant, splice_region_variant	37/39		NM_001377321.1	ENSP00000509702.1	Q8WWZ4-1
ABCA10	ENST00000522406.5 linkuse as main transcript	n.*3326A>T		splice_region_variant, non_coding_transcript_exon_variant	39/41	1		ENSP00000429853.1	Q8WWZ4-5
ABCA10	ENST00000522406.5 linkuse as main transcript	n.*3326A>T		3_prime_UTR_variant	39/41	1		ENSP00000429853.1	Q8WWZ4-5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000522

AC:

AN:

248858

Hom.:

AF XY:

0.0000670

AC XY:

AN XY:

134426

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000657

Gnomad SAS exome

AF:

0.0000336

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1455604

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

724342

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000303

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000576

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

Jan 30, 2024

The c.4398A>T (p.R1466S) alteration is located in exon 38 (coding exon 35) of the ABCA10 gene. This alteration results from a A to T substitution at nucleotide position 4398, causing the arginine (R) at amino acid position 1466 to be replaced by a serine (S). 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

0.28

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.035

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.049

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.025

MetaRNN

Benign

0.056

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.32

Sift

Benign

0.30

Sift4G

Benign

0.44

Polyphen

1.0

Vest4

0.16

MutPred

0.42

Gain of phosphorylation at Y1467 (P = 0.0991);

MVP

0.37

MPC

0.15

ClinPred

0.11

GERP RS

-2.4

Varity_R

0.23

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00061

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.020

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