7-151034384-T-C

Variant names:

• chr7-151034384-T-C
• NM_007188.5:c.520T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_007188.5(ABCB8):​c.520T>C​(p.Ser174Pro) 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 pathogenic outcome for this variant. 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: 2.84
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.520T>C	p.Ser174Pro	missense_variant	Exon 3 of 16	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.571T>C	p.Ser191Pro	missense_variant	Exon 4 of 17		NP_001269220.1
ABCB8	NM_001282292.2	c.520T>C	p.Ser174Pro	missense_variant	Exon 3 of 16		NP_001269221.1
ABCB8	NM_001282293.2	c.256T>C	p.Ser86Pro	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.520T>C	p.Ser174Pro	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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 30, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.520T>C (p.S174P) alteration is located in exon 3 (coding exon 3) of the ABCB8 gene. This alteration results from a T to C substitution at nucleotide position 520, causing the serine (S) at amino acid position 174 to be replaced by a proline (P). 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	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;.;T;.;.;T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;D;D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Benign	0.17	.;.;N;.;.;.
PhyloP100		2.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N
REVEL	Uncertain	0.58
Sift	Benign	0.21	T;T;T;T;D;T
Sift4G	Benign	0.25	T;T;T;T;D;D
Polyphen		0.41, 0.46, 0.84	.;B;P;.;.;P
Vest4		0.77
MutPred		0.62		.;.;Gain of loop (P = 0.0851);.;.;.;
MVP		0.98
MPC		0.49
ClinPred		0.56	D
GERP RS		2.6
Varity_R		0.52
gMVP		0.92
Mutation Taster		=60/40	polymorphism

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

hg19: chr7-150731471;