Variant 3-140976331-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001104647.3(SLC25A36):c.814G>T(p.Val272Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SLC25A36
NM_001104647.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

Variant links:

Genes affected

SLC25A36 (HGNC:25554): (solute carrier family 25 member 36) Enables pyrimidine nucleotide transmembrane transporter activity. Involved in mitochondrial genome maintenance; pyrimidine nucleotide transport; and regulation of mitochondrial membrane potential. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A36 links:

SLC25A36 (HGNC:):

SLC25A36 links:

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ACMG classification

Classification made for transcript

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=0.1370734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A36	NM_001104647.3 linkuse as main transcript	c.814G>T	p.Val272Phe	missense_variant	7/7	ENST00000324194.12	NP_001098117.1	Q96CQ1-1A0A384MEA9
SLC25A36	NM_018155.3 linkuse as main transcript	c.811G>T	p.Val271Phe	missense_variant	7/7		NP_060625.2	Q96CQ1-3
SLC25A36	XM_047448440.1 linkuse as main transcript	c.910G>T	p.Val304Phe	missense_variant	7/7		XP_047304396.1
SLC25A36	XM_005247575.6 linkuse as main transcript	c.445G>T	p.Val149Phe	missense_variant	5/5		XP_005247632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A36	ENST00000324194.12 linkuse as main transcript	c.814G>T	p.Val272Phe	missense_variant	7/7	1	NM_001104647.3	ENSP00000320688.6		Q96CQ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250906

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461448

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.814G>T (p.V272F) alteration is located in exon 7 (coding exon 7) of the SLC25A36 gene. This alteration results from a G to T substitution at nucleotide position 814, causing the valine (V) at amino acid position 272 to be replaced by a phenylalanine (F). 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

0.093

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.13

.;T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.032

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.27

.;N;.

PrimateAI

Benign

0.47

PROVEAN

Benign

2.0

N;N;N

REVEL

Benign

0.24

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.40

MVP

0.42

MPC

0.90

ClinPred

0.050

GERP RS

4.3

Varity_R

0.080

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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