X-104104362-T-G

Variant names:

• chrX-104104362-T-G
• rs144228809
• NM_001012755.5:c.896A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012755.5(SLC25A53):​c.896A>C​(p.His299Pro) 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. 14/19 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. H299L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC25A53 NM_001012755.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06725681).

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.896A>C	p.His299Pro	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.896A>C	p.His299Pro	missense	Exon 2 of 2	ENSP00000468980.1	Q5H9E4
	SLC25A53	ENST00000905741.1		c.896A>C	p.His299Pro	missense	Exon 3 of 3	ENSP00000575800.1
	SLC25A53	ENST00000905742.1		c.896A>C	p.His299Pro	missense	Exon 3 of 3	ENSP00000575801.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.12e-7 AC: 1 AN: 1096867 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1 AN XY: 362461

African (AFR) AF: 0.00 AC: 0 AN: 26376

American (AMR) AF: 0.00 AC: 0 AN: 35181

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19329

East Asian (EAS) AF: 0.00 AC: 0 AN: 30187

South Asian (SAS) AF: 0.00 AC: 0 AN: 54080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40521

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3821

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841359

Other (OTH) AF: 0.00 AC: 0 AN: 46013

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.088
DANN	Benign	0.52
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.17
PrimateAI	Benign	0.36	T
Sift4G	Benign	0.31	T
Polyphen		0.026	B
Vest4		0.16
MutPred		0.42		Gain of glycosylation at H299 (P = 0.0023)
MVP		0.19
ClinPred		0.040	T
GERP RS		-2.9
Varity_R		0.076
gMVP		0.96
Mutation Taster		=99/1	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: rs144228809; hg19: chrX-103349045;