rs151194300

Variant names:

• chr7-151035594-G-A
• rs151194300
• NM_007188.5:c.779G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-151035594-G-A
• chr7-151035594-G-C

Variant summary

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

The NM_007188.5(ABCB8):​c.779G>A​(p.Cys260Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C260S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCB8 NM_007188.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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=0.29407915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.779G>A	p.Cys260Tyr	missense_variant	Exon 6 of 16	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.830G>A	p.Cys277Tyr	missense_variant	Exon 7 of 17		NP_001269220.1
ABCB8	NM_001282292.2	c.779G>A	p.Cys260Tyr	missense_variant	Exon 6 of 16		NP_001269221.1
ABCB8	NM_001282293.2	c.515G>A	p.Cys172Tyr	missense_variant	Exon 5 of 15		NP_001269222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB8	ENST00000358849.9	c.779G>A	p.Cys260Tyr	missense_variant	Exon 6 of 16	1	NM_007188.5	ENSP00000351717.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1448576 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 717944

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.23	.;.;T;.;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.29	T;T;T;T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.7	.;.;L;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.25	N;N;N;N;N;N
REVEL	Uncertain	0.36
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;D;D
Polyphen		0.069, 0.15, 0.24	.;B;B;.;.;B
Vest4		0.51
MVP		0.89
MPC		0.42
ClinPred		0.27	T
GERP RS		3.0
Varity_R		0.052
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs151194300; hg19: chr7-150732681; COSMIC: COSV52503820; COSMIC: COSV52503820;