chr7-151035888-A-G

Position:

• chr7-151035888-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007188.5(ABCB8):​c.934A>G​(p.Arg312Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCB8 NM_007188.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.99

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB8	NM_007188.5	c.934A>G	p.Arg312Gly	missense_variant	7/16	ENST00000358849.9
ABCB8	NM_001282291.2	c.985A>G	p.Arg329Gly	missense_variant	8/17
ABCB8	NM_001282292.2	c.934A>G	p.Arg312Gly	missense_variant	7/16
ABCB8	NM_001282293.2	c.670A>G	p.Arg224Gly	missense_variant	6/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB8	ENST00000358849.9	c.934A>G	p.Arg312Gly	missense_variant	7/16	1	NM_007188.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2023

The c.934A>G (p.R312G) alteration is located in exon 7 (coding exon 7) of the ABCB8 gene. This alteration results from a A to G substitution at nucleotide position 934, causing the arginine (R) at amino acid position 312 to be replaced by a glycine (G). 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	0.13
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.53	.;.;D;.;.;D
Eigen	Benign	-0.089
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D
MetaSVM	Uncertain	-0.048	T
MutationAssessor	Benign	1.1	.;.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D;D
REVEL	Uncertain	0.53
Sift	Benign	0.12	T;D;T;D;D;D
Sift4G	Benign	0.14	T;T;T;T;D;D
Polyphen		0.13, 0.39, 0.61	.;B;B;.;.;P
Vest4		0.47
MutPred		0.51		.;.;Loss of MoRF binding (P = 0.0076);.;.;.;
MVP		0.95
MPC		0.31
ClinPred		0.74	D
GERP RS		3.9
Varity_R		0.21
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr7-150732975;