rs761183980

Variant names:

• chr19-6454335-C-A
• rs761183980
• NM_024103.3:c.783G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-6454335-C-A
• chr19-6454335-C-T

Variant summary

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

The NM_024103.3(SLC25A23):​c.783G>T​(p.Met261Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A23 NM_024103.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86

Genes affected

SLC25A23 (HGNC:19375): (solute carrier family 25 member 23) Predicted to enable ATP transmembrane transporter activity. Involved in calcium import into the mitochondrion; positive regulation of mitochondrial calcium ion concentration; and regulation of cellular hyperosmotic salinity response. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
SLC25A23	NM_024103.3	c.783G>T	p.Met261Ile	missense_variant	Exon 6 of 10	ENST00000301454.9	NP_077008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A23	ENST00000301454.9	c.783G>T	p.Met261Ile	missense_variant	Exon 6 of 10	1	NM_024103.3	ENSP00000301454.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	.;D;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.42	T;D;D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.2	.;L;L
PhyloP100		2.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	.;N;D
REVEL	Uncertain	0.39
Sift	Benign	0.21	.;T;T
Sift4G	Uncertain	0.012	D;T;T
Polyphen		0.58	.;P;.
Vest4		0.63, 0.64
MutPred		0.63		.;Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.53
MPC		0.62
ClinPred		0.76	D
GERP RS		5.8
PromoterAI		-0.020	Neutral
Varity_R		0.31
gMVP		0.86
Mutation Taster		=48/52	disease causing

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: rs761183980; hg19: chr19-6454346; COSMIC: COSV51195835; COSMIC: COSV51195835;