NM_007188.5:c.226G>C

Variant names:

• chr7-151033735-G-C
• rs1796227143
• NM_007188.5:c.226G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007188.5(ABCB8):​c.226G>C​(p.Gly76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB8 NM_007188.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.226G>C	p.Gly76Arg	missense_variant	Exon 2 of 16	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.277G>C	p.Gly93Arg	missense_variant	Exon 3 of 17		NP_001269220.1
ABCB8	NM_001282292.2	c.226G>C	p.Gly76Arg	missense_variant	Exon 2 of 16		NP_001269221.1
ABCB8	NM_001282293.2	c.145-538G>C		intron_variant	Intron 1 of 14		NP_001269222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB8	ENST00000358849.9	c.226G>C	p.Gly76Arg	missense_variant	Exon 2 of 16	1	NM_007188.5	ENSP00000351717.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	.;.;T;.;.;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	1.9	.;.;L;.;.;.
PhyloP100		2.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-7.9	D;N;N;N;N;N
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D
Polyphen		0.97, 0.99	.;D;D;.;.;D
Vest4		0.54, 0.51, 0.56, 0.41, 0.47
MutPred		0.57		.;.;Gain of MoRF binding (P = 0.0031);.;.;.;
MVP		0.91
MPC		0.70
ClinPred		1.0	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.47
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1796227143; hg19: chr7-150730822;