Genetic Variant NM_001377321.1:c.4117G>C (chr17-69153324-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001377321.1(ABCA10):c.4117G>C(p.Glu1373Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Consequence

ABCA10
NM_001377321.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.157

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2917687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA10	NM_001377321.1 link	c.4117G>C	p.Glu1373Gln	missense_variant	Exon 34 of 39	ENST00000690296.1	NP_001364250.1
ABCA10	NM_080282.4 link	c.4117G>C	p.Glu1373Gln	missense_variant	Exon 35 of 40		NP_525021.3	Q8WWZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCA10	ENST00000690296.1 link	c.4117G>C	p.Glu1373Gln	missense_variant	Exon 34 of 39		NM_001377321.1	ENSP00000509702.1	Q8WWZ4-1
ABCA10	ENST00000522406.5 link	n.*3045G>C		non_coding_transcript_exon_variant	Exon 36 of 41	1		ENSP00000429853.1	Q8WWZ4-5
ABCA10	ENST00000522406.5 link	n.*3045G>C		3_prime_UTR_variant	Exon 36 of 41	1		ENSP00000429853.1	Q8WWZ4-5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

CADD

Benign

7.5

DANN

Benign

0.90

DEOGEN2

Benign

0.0053

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.15

M_CAP

Benign

0.058

MetaRNN

Benign

0.29

MetaSVM

Uncertain

0.17

MutationAssessor

Benign

0.13

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.35

Sift

Benign

0.10

Sift4G

Benign

0.061

Polyphen

0.99

Vest4

0.23

MutPred

0.34

Loss of glycosylation at P1372 (P = 0.1235);

MVP

0.58

MPC

0.035

ClinPred

0.21

GERP RS

-1.1

Varity_R

0.060

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over