chr7-151028535-G-T

Position:

• chr7-151028535-G-T

Variant summary

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

The NM_007188.5(ABCB8):​c.20G>T​(p.Arg7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 3.00

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.20G>T	p.Arg7Leu	missense_variant	1/16	ENST00000358849.9
ABCB8	NM_001282291.2	c.20G>T	p.Arg7Leu	missense_variant	1/17
ABCB8	NM_001282292.2	c.20G>T	p.Arg7Leu	missense_variant	1/16
ABCB8	NM_001282293.2	c.69G>T	p.Ser23=	synonymous_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB8	ENST00000358849.9	c.20G>T	p.Arg7Leu	missense_variant	1/16	1	NM_007188.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000340

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

Oct 12, 2022

The c.20G>T (p.R7L) alteration is located in exon 1 (coding exon 1) of the ABCB8 gene. This alteration results from a G to T substitution at nucleotide position 20, causing the arginine (R) at amino acid position 7 to be replaced by a leucine (L). 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	0.31
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	.;.;T;.;.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Benign	1.9	.;L;L;L;.;.
MutationTaster	Benign	0.91	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-7.0	D;N;N;N;N;N
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	.;D;D;.;.;D
Vest4		0.64, 0.55, 0.65, 0.64, 0.68
MutPred		0.45		Loss of MoRF binding (P = 1e-04);Loss of MoRF binding (P = 1e-04);Loss of MoRF binding (P = 1e-04);Loss of MoRF binding (P = 1e-04);Loss of MoRF binding (P = 1e-04);Loss of MoRF binding (P = 1e-04);
MVP		0.91
MPC		0.93
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.41

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: rs750232334; hg19: chr7-150725622; COSMIC: COSV99875211; COSMIC: COSV99875211;