Variant 7-151035644-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_007188.5(ABCB8):c.829C>G(p.Leu277Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ABCB8
NM_007188.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB8	NM_007188.5 linkuse as main transcript	c.829C>G	p.Leu277Val	missense_variant	6/16	ENST00000358849.9	NP_009119.2	Q9NUT2-2
ABCB8	NM_001282291.2 linkuse as main transcript	c.880C>G	p.Leu294Val	missense_variant	7/17		NP_001269220.1	Q9NUT2-1
ABCB8	NM_001282292.2 linkuse as main transcript	c.829C>G	p.Leu277Val	missense_variant	6/16		NP_001269221.1	Q9NUT2-3
ABCB8	NM_001282293.2 linkuse as main transcript	c.565C>G	p.Leu189Val	missense_variant	5/15		NP_001269222.1	Q9NUT2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB8	ENST00000358849.9 linkuse as main transcript	c.829C>G	p.Leu277Val	missense_variant	6/16	1	NM_007188.5	ENSP00000351717.4		Q9NUT2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460510

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726398

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Aug 04, 2023

The c.829C>G (p.L277V) alteration is located in exon 6 (coding exon 6) of the ABCB8 gene. This alteration results from a C to G substitution at nucleotide position 829, causing the leucine (L) at amino acid position 277 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

Pathogenic

0.60

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

.;.;D;.;.;D

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D;D;D;D;D

M_CAP

Pathogenic

0.30

MetaRNN

Pathogenic

0.86

D;D;D;D;D;D

MetaSVM

Uncertain

-0.074

MutationAssessor

Pathogenic

3.5

.;.;M;.;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.3

N;N;N;N;N;N

REVEL

Pathogenic

0.86

Sift

Uncertain

0.021

D;D;D;D;D;D

Sift4G

Uncertain

0.037

D;D;D;D;D;D

Polyphen

1.0

.;D;D;.;.;D

Vest4

0.71

MutPred

0.80

.;.;Gain of methylation at R293 (P = 0.1108);.;.;.;

MVP

0.99

MPC

0.80

ClinPred

0.99

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.81

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over