X-104104882-C-T

Variant names:

• chrX-104104882-C-T
• rs112530678
• NM_001012755.5:c.376G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001012755.5(SLC25A53):​c.376G>A​(p.Val126Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,210,107 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 57 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V126L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., 4 hem., cov: 23)
  • Exomes 𝑓: 0.00014 (0 hom. 53 hem.)
• Consequence: SLC25A53 NM_001012755.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017049938).
• BS2: High Hemizygotes in GnomAd4 at 4 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.376G>A	p.Val126Met	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.376G>A	p.Val126Met	missense	Exon 2 of 2	ENSP00000468980.1	Q5H9E4
	SLC25A53	ENST00000905741.1		c.376G>A	p.Val126Met	missense	Exon 3 of 3	ENSP00000575800.1
	SLC25A53	ENST00000905742.1		c.376G>A	p.Val126Met	missense	Exon 3 of 3	ENSP00000575801.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 22 AN: 111885 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000976

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000189

Gnomad ASJ AF: 0.00567

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000246 AC: 45 AN: 183061 AF XY: 0.000266

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00375

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000137 AC: 150 AN: 1098222 Hom.: 0 Cov.: 32 AF XY: 0.000146 AC XY: 53 AN XY: 363582

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.000199 AC: 7 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00340 AC: 66 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54145

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40529

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.0000689 AC: 58 AN: 842121

Other (OTH) AF: 0.000412 AC: 19 AN: 46095

GnomAD4 genome AF: 0.000197 AC: 22 AN: 111885 Hom.: 0 Cov.: 23 AF XY: 0.000118 AC XY: 4 AN XY: 34035

African (AFR) AF: 0.0000976 AC: 3 AN: 30732

American (AMR) AF: 0.000189 AC: 2 AN: 10579

Ashkenazi Jewish (ASJ) AF: 0.00567 AC: 15 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.00 AC: 0 AN: 2676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53223

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.000612 Hom.: 6

Bravo AF: 0.000174

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.20
PrimateAI	Benign	0.48	T
Sift4G	Uncertain	0.033	D
Polyphen		0.80	P
Vest4		0.13
MVP		0.51
ClinPred		0.039	T
GERP RS		2.4
Varity_R		0.048
gMVP		0.49

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: rs112530678; hg19: chrX-103349565; COSMIC: COSV100655940;