rs782093486

Variant names:

• chrX-104104356-C-A
• rs782093486
• NM_001012755.5:c.902G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-104104356-C-A
• chrX-104104356-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001012755.5(SLC25A53):​c.902G>T​(p.Arg301Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,097,053 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. 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. R301K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000045 (0 hom. 14 hem.)
• Consequence: SLC25A53 NM_001012755.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.698
• Publications: 4 publications found

Genes affected

SLC25A53 (HGNC:31894): (solute carrier family 25 member 53) Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10779855).
• BS2: High Hemizygotes in GnomAdExome4 at 14 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012755.5. 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
	SLC25A53	NM_001012755.5	MANE Select	c.902G>T	p.Arg301Met	missense	Exon 2 of 2	NP_001012773.2	Q5H9E4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A53	ENST00000594199.3	TSL:1 MANE Select	c.902G>T	p.Arg301Met	missense	Exon 2 of 2	ENSP00000468980.1	Q5H9E4
	SLC25A53	ENST00000905741.1		c.902G>T	p.Arg301Met	missense	Exon 3 of 3	ENSP00000575800.1
	SLC25A53	ENST00000905742.1		c.902G>T	p.Arg301Met	missense	Exon 3 of 3	ENSP00000575801.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00000548 AC: 1 AN: 182532 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000447 AC: 49 AN: 1097053 Hom.: 0 Cov.: 30 AF XY: 0.0000386 AC XY: 14 AN XY: 362679

African (AFR) AF: 0.00 AC: 0 AN: 26372

American (AMR) AF: 0.00 AC: 0 AN: 35183

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19320

East Asian (EAS) AF: 0.00 AC: 0 AN: 30191

South Asian (SAS) AF: 0.00 AC: 0 AN: 54065

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3806

European-Non Finnish (NFE) AF: 0.0000582 AC: 49 AN: 841575

Other (OTH) AF: 0.00 AC: 0 AN: 46021

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000346 AC: 1

ExAC AF: 0.00000824 AC: 1

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	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.2
DANN	Benign	0.95
DEOGEN2	Benign	0.0068	T
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.70
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.33	B
Vest4		0.33
MVP		0.23
ClinPred		0.37	T
GERP RS		0.43
Varity_R		0.089
gMVP		0.82
Mutation Taster		=100/0	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

dbSNP: rs782093486; hg19: chrX-103349039; COSMIC: COSV62460091;