Variant 7-151033748-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007188.5(ABCB8):c.239G>T(p.Gly80Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

ABCB8
NM_007188.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.50

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24451771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABCB8	NM_007188.5 linkuse as main transcript	c.239G>T	p.Gly80Val	missense_variant	2/16	ENST00000358849.9
ABCB8	NM_001282291.2 linkuse as main transcript	c.290G>T	p.Gly97Val	missense_variant	3/17
ABCB8	NM_001282292.2 linkuse as main transcript	c.239G>T	p.Gly80Val	missense_variant	2/16
ABCB8	NM_001282293.2 linkuse as main transcript	c.145-525G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB8	ENST00000358849.9 linkuse as main transcript	c.239G>T	p.Gly80Val	missense_variant	2/16	1	NM_007188.5	P1	Q9NUT2-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

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

May 18, 2023

The c.239G>T (p.G80V) alteration is located in exon 2 (coding exon 2) of the ABCB8 gene. This alteration results from a G to T substitution at nucleotide position 239, causing the glycine (G) at amino acid position 80 to be replaced by a valine (V). 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

0.094

BayesDel_addAF

Benign

0.0035

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.88

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.82

T;T;T;T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.24

T;T;T;T;T;T

MetaSVM

Benign

-0.44

MutationTaster

Benign

0.91

N;N;N;N;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.7

D;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.21

T;T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T;T

Polyphen

0.46, 0.052, 0.022

.;P;B;.;.;B

Vest4

0.28, 0.29, 0.33, 0.30, 0.31

MutPred

0.64

.;.;Loss of loop (P = 0.0804);.;.;.;

MVP

0.95

MPC

0.33

ClinPred

0.60

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.041

gMVP

0.67

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