NM_007188.5:c.430G>C

Variant names:

• chr7-151034294-G-C
• rs150872185
• NM_007188.5:c.430G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007188.5(ABCB8):​c.430G>C​(p.Val144Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCB8 NM_007188.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27253145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.430G>C	p.Val144Leu	missense_variant	Exon 3 of 16	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.481G>C	p.Val161Leu	missense_variant	Exon 4 of 17		NP_001269220.1
ABCB8	NM_001282292.2	c.430G>C	p.Val144Leu	missense_variant	Exon 3 of 16		NP_001269221.1
ABCB8	NM_001282293.2	c.166G>C	p.Val56Leu	missense_variant	Exon 2 of 15		NP_001269222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB8	ENST00000358849.9	c.430G>C	p.Val144Leu	missense_variant	Exon 3 of 16	1	NM_007188.5	ENSP00000351717.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;.;T;.;.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.27	T;T;T;T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	-0.25	.;.;N;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.91	N;N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.61	T;T;T;T;T;T
Sift4G	Benign	0.71	T;T;T;T;T;T
Polyphen		0.0090, 0.022, 0.087	.;B;B;.;.;B
Vest4		0.38
MutPred		0.70		.;.;Loss of catalytic residue at V161 (P = 0.0297);.;.;.;
MVP		0.88
MPC		0.22
ClinPred		0.58	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.080
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs150872185; hg19: chr7-150731381;