rs104893873

Variant names:

• chr4-185144992-G-A
• NM_001151.4:c.340G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-185144992-G-A
• chr4-185144992-G-C
• chr4-185144992-G-T

Variant summary

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

The NM_001151.4(SLC25A4):​c.340G>A​(p.Ala114Thr) variant causes a missense change involving the alteration of a 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: 32)
• Consequence: SLC25A4 NM_001151.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0

Genes affected

SLC25A4 (HGNC:10990): (solute carrier family 25 member 4) This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein forms a homodimer embedded in the inner mitochondria membrane. Mutations in this gene have been shown to result in autosomal dominant progressive external opthalmoplegia and familial hypertrophic cardiomyopathy. [provided by RefSeq, Jun 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 rank	MANE	Protein	UniProt
SLC25A4	NM_001151.4	c.340G>A	p.Ala114Thr	missense_variant	Exon 2 of 4	ENST00000281456.11	NP_001142.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A4	ENST00000281456.11	c.340G>A	p.Ala114Thr	missense_variant	Exon 2 of 4	1	NM_001151.4	ENSP00000281456.5
SLC25A4	ENST00000491736.1	n.340G>A		non_coding_transcript_exon_variant	Exon 2 of 4	5		ENSP00000476711.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.340G>A (p.A114T) alteration is located in exon 2 (coding exon 2) of the SLC25A4 gene. This alteration results from a G to A substitution at nucleotide position 340, causing the alanine (A) at amino acid position 114 to be replaced by a threonine (T). 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	0.25
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.7	L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.088	T
Polyphen		0.0070	B
Vest4		0.73
MutPred		0.49		Loss of catalytic residue at A114 (P = 0.0173);
MVP		0.83
MPC		0.95
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.51
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-186066146;