chrX-104105219-C-A

Variant names:

• chrX-104105219-C-A
• NM_001012755.5:c.39G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012755.5(SLC25A53):​c.39G>T​(p.Gln13His) 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 benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLC25A53 NM_001012755.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.117
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09724572).

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.39G>T	p.Gln13His	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.39G>T	p.Gln13His	missense	Exon 2 of 2	ENSP00000468980.1	Q5H9E4
	SLC25A53	ENST00000905741.1		c.39G>T	p.Gln13His	missense	Exon 3 of 3	ENSP00000575800.1
	SLC25A53	ENST00000905742.1		c.39G>T	p.Gln13His	missense	Exon 3 of 3	ENSP00000575801.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

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	0.099
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.12
PrimateAI	Uncertain	0.53	T
Sift4G	Uncertain	0.010	D
Polyphen		0.84	P
Vest4		0.16
MutPred		0.15		Loss of MoRF binding (P = 0.0918)
MVP		0.20
ClinPred		0.45	T
GERP RS		3.7
Varity_R		0.10
gMVP		0.62
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

hg19: chrX-103349902;