Variant 7-151033645-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_007188.5(ABCB8):c.136G>A(p.Val46Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,601,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

ABCB8
NM_007188.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.632

Variant links:

Genes affected

ABCB8 (HGNC:49): (ATP binding cassette subfamily B member 8) This nuclear gene encodes a multi-pass membrane protein that is targeted to the mitochondrial inner membrane. The encoded protein is an ATP-dependent transporter that may mediate the passage of organic and inorganic molecules out of the mitochondria. Loss of function of the related gene in mouse results in a disruption of iron homeostasis between the mitochondria and cytosol. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ABCB8 links:

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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=0.014907926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5 link	c.136G>A	p.Val46Met	missense_variant	Exon 2 of 16	ENST00000358849.9	NP_009119.2	Q9NUT2-2
ABCB8	NM_001282291.2 link	c.187G>A	p.Val63Met	missense_variant	Exon 3 of 17		NP_001269220.1	Q9NUT2-1
ABCB8	NM_001282292.2 link	c.136G>A	p.Val46Met	missense_variant	Exon 2 of 16		NP_001269221.1	Q9NUT2-3
ABCB8	NM_001282293.2 link	c.145-628G>A		intron_variant	Intron 1 of 14		NP_001269222.1	Q9NUT2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB8	ENST00000358849.9 link	c.136G>A	p.Val46Met	missense_variant	Exon 2 of 16	1	NM_007188.5	ENSP00000351717.4		Q9NUT2-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000963

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:

0.0000660

AC:

AN:

242522

Hom.:

AF XY:

0.0000609

AC XY:

AN XY:

131396

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000494

Gnomad SAS exome

AF:

0.0000670

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000369

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000759

AC:

110

AN:

1449060

Hom.:

Cov.:

AF XY:

0.0000709

AC XY:

AN XY:

719098

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00165

Gnomad4 SAS exome

AF:

0.0000937

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000263

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.136G>A (p.V46M) alteration is located in exon 2 (coding exon 2) of the ABCB8 gene. This alteration results from a G to A substitution at nucleotide position 136, causing the valine (V) at amino acid position 46 to be replaced by a methionine (M). 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

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.69

DANN

Benign

0.63

DEOGEN2

Benign

0.053

.;.;T;.;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.81

T;T;T;T;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.015

T;T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.1

.;.;L;.;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.22

T;T;T;T;T;T

Sift4G

Benign

0.47

T;T;T;T;T;T

Polyphen

0.028, 0.016, 0.041

.;B;B;.;.;B

Vest4

0.086, 0.090, 0.14, 0.15, 0.14

MutPred

0.22

.;.;Gain of disorder (P = 0.0551);.;.;.;

MVP

0.42

MPC

0.22

ClinPred

0.011

GERP RS

-6.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

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