NM_007188.5:c.605T>C

Variant names:

• chr7-151034545-T-C
• rs1249215292
• NM_007188.5:c.605T>C

Variant summary

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

The NM_007188.5(ABCB8):​c.605T>C​(p.Val202Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,312 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V202I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ABCB8 NM_007188.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.37
• Publications: 1 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007188.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB8	NM_007188.5	MANE Select	c.605T>C	p.Val202Ala	missense	Exon 4 of 16	NP_009119.2	Q9NUT2-2
	ABCB8	NM_001282291.2		c.656T>C	p.Val219Ala	missense	Exon 5 of 17	NP_001269220.1	Q9NUT2-1
	ABCB8	NM_001282292.2		c.605T>C	p.Val202Ala	missense	Exon 4 of 16	NP_001269221.1	Q9NUT2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB8	ENST00000358849.9	TSL:1 MANE Select	c.605T>C	p.Val202Ala	missense	Exon 4 of 16	ENSP00000351717.4	Q9NUT2-2
	ABCB8	ENST00000498578.5	TSL:1	c.605T>C	p.Val202Ala	missense	Exon 4 of 16	ENSP00000418271.1	Q9NUT2-3
	ABCB8	ENST00000879589.1		c.737T>C	p.Val246Ala	missense	Exon 5 of 17	ENSP00000549648.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461312 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726988

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.074
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	-0.074	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.4
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.41
Sift	Benign	0.26	T
Sift4G	Benign	0.59	T
Polyphen		0.0080	B
Vest4		0.50
MutPred		0.75		Loss of stability (P = 0.0652)
MVP		0.96
MPC		0.29
ClinPred		0.86	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.66
Mutation Taster		=37/63	disease causing

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

Other links and lift over

dbSNP: rs1249215292; hg19: chr7-150731632; COSMIC: COSV52508107; COSMIC: COSV52508107;