X-119470067-T-C

Position:

chrX-119470067-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP3BP4BP6BS1

The NM_001152.5(SLC25A5):c.518T>C(p.Leu173Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000975 in 1,008,679 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.016 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.00015 ( 0 hom. 0 hem. )

Consequence

SLC25A5
NM_001152.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 7.68

Variant links:

Genes affected

SLC25A5 (HGNC:10991): (solute carrier family 25 member 5) This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein forms a homodimer embedded in the inner mitochondria membrane. Suppressed expression of this gene has been shown to induce apoptosis and inhibit tumor growth. The human genome contains several non-transcribed pseudogenes of this gene.[provided by RefSeq, Jun 2013]

SLC25A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, M_CAP, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.30138046).

BP6

Variant X-119470067-T-C is Benign according to our data. Variant chrX-119470067-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0164 (844/51451) while in subpopulation AFR AF= 0.0232 (288/12400). AF 95% confidence interval is 0.021. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A5	NM_001152.5 linkuse as main transcript	c.518T>C	p.Leu173Pro	missense_variant	2/4	ENST00000317881.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC25A5	ENST00000317881.9 linkuse as main transcript	c.518T>C	p.Leu173Pro	missense_variant	2/4	1	NM_001152.5	P1
SLC25A5	ENST00000460013.1 linkuse as main transcript	n.514T>C		non_coding_transcript_exon_variant	2/4	3
SLC25A5	ENST00000475354.1 linkuse as main transcript	n.395T>C		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

844

AN:

51456

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

7942

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.00741

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.0158

Gnomad EAS

AF:

0.00179

Gnomad SAS

AF:

0.00910

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.00820

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0242

GnomAD4 exome

AF:

0.000145

AC:

139

AN:

957228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

264064

show subpopulations

Gnomad4 AFR exome

AF:

0.000225

Gnomad4 AMR exome

AF:

0.000212

Gnomad4 ASJ exome

AF:

0.000257

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000916

Gnomad4 FIN exome

AF:

0.00243

Gnomad4 NFE exome

AF:

0.0000575

Gnomad4 OTH exome

AF:

0.000127

GnomAD4 genome

AF:

0.0164

AC:

844

AN:

51451

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

7945

show subpopulations

Gnomad4 AFR

AF:

0.0232

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.0158

Gnomad4 EAS

AF:

0.00178

Gnomad4 SAS

AF:

0.00922

Gnomad4 FIN

AF:

0.0162

Gnomad4 NFE

AF:

0.0144

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.103

Hom.:

ExAC

AF:

0.00133

AC:

161

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Small cell lung carcinoma

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

- -

Lung cancer

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.58

BayesDel_noAF

Pathogenic

0.59

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.79

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.30

MetaSVM

Pathogenic

0.97

MutationAssessor

Pathogenic

4.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.3

REVEL

Pathogenic

0.94

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.99

MVP

1.0

MPC

3.0

ClinPred

1.0

GERP RS

4.3

Varity_R

0.98

gMVP

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over