chr7-151033645-G-A

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

19

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]

Genome browser will be placed here

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/exons MANE UniProt
ABCB8NM_007188.5 linkuse as main transcriptc.136G>A p.Val46Met missense_variant 2/16 ENST00000358849.9
ABCB8NM_001282291.2 linkuse as main transcriptc.187G>A p.Val63Met missense_variant 3/17
ABCB8NM_001282292.2 linkuse as main transcriptc.136G>A p.Val46Met missense_variant 2/16
ABCB8NM_001282293.2 linkuse as main transcriptc.145-628G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCB8ENST00000358849.9 linkuse as main transcriptc.136G>A p.Val46Met missense_variant 2/161 NM_007188.5 P1Q9NUT2-2

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152170
Hom.:
0
Cov.:
32
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:
16
AN:
242522
Hom.:
0
AF XY:
0.0000609
AC XY:
8
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.:
0
Cov.:
30
AF XY:
0.0000709
AC XY:
51
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:
7
AN:
152288
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
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.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsDec 14, 2022The 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
T
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
N
LIST_S2
Benign
0.81
T;T;T;T;T;T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.015
T;T;T;T;T;T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
1.1
.;.;L;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PrimateAI
Benign
0.42
T
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
T
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.

Other links and lift over

dbSNP: rs566864336; hg19: chr7-150730732; COSMIC: COSV52502155; COSMIC: COSV52502155; API