X-104105219-C-A

Position:

• chrX-104105219-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 11/18 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A53	NM_001012755.5	c.39G>T	p.Gln13His	missense_variant	2/2	ENST00000594199.3	NP_001012773.2
SLC25A53	XM_005262129.6	c.39G>T	p.Gln13His	missense_variant	2/2		XP_005262186.1
SLC25A53	XM_011530952.4	c.39G>T	p.Gln13His	missense_variant	3/3		XP_011529254.1
SLC25A53	XM_011530953.4	c.39G>T	p.Gln13His	missense_variant	3/3		XP_011529255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A53	ENST00000594199.3	c.39G>T	p.Gln13His	missense_variant	2/2	1	NM_001012755.5	ENSP00000468980.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.39G>T (p.Q13H) alteration is located in exon 2 (coding exon 1) of the SLC25A53 gene. This alteration results from a G to T substitution at nucleotide position 39, causing the glutamine (Q) at amino acid position 13 to be replaced by a histidine (H). 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	0.099
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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-103349902;