Genetic Variant NM_001377321.1:c.4429G>T (chr17-69150032-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001377321.1(ABCA10):c.4429G>T(p.Val1477Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ABCA10
NM_001377321.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.318

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1268411).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377321.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA10	NM_001377321.1	MANE Select	c.4429G>T	p.Val1477Leu	missense	Exon 37 of 39	NP_001364250.1	Q8WWZ4-1
	ABCA10	NM_080282.4		c.4429G>T	p.Val1477Leu	missense	Exon 38 of 40	NP_525021.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCA10	ENST00000690296.1	MANE Select	c.4429G>T	p.Val1477Leu	missense	Exon 37 of 39	ENSP00000509702.1	Q8WWZ4-1
ABCA10	ENST00000269081.8	TSL:1	c.4429G>T	p.Val1477Leu	missense	Exon 38 of 40	ENSP00000269081.4	Q8WWZ4-1
ABCA10	ENST00000518929.5	TSL:1	n.*3830G>T		non_coding_transcript_exon	Exon 33 of 35	ENSP00000430341.1	E5RFP5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152090

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

250952

AF XY:

0.00000737

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461030

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726830

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1111444

Other (OTH)

AF:

0.0000166

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.063

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0033

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.72

M_CAP

Benign

0.0076

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.7

PhyloP100

-0.32

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.8

REVEL

Benign

0.11

Sift

Benign

0.25

Sift4G

Benign

0.071

Polyphen

0.044

Vest4

0.14

MutPred

0.29

Loss of sheet (P = 0.0126)

MVP

0.46

MPC

0.029

ClinPred

0.059

GERP RS

2.2

PromoterAI

-0.0033

Neutral

(source)

Varity_R

0.062

gMVP

0.14

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over