Variant 3-140942085-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001104647.3(SLC25A36):c.31T>C(p.Phe11Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000081 in 1,468,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

SLC25A36
NM_001104647.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4117604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A36	NM_001104647.3 linkuse as main transcript	c.31T>C	p.Phe11Leu	missense_variant	1/7	ENST00000324194.12	NP_001098117.1	Q96CQ1-1A0A384MEA9
SLC25A36	NM_018155.3 linkuse as main transcript	c.31T>C	p.Phe11Leu	missense_variant	1/7		NP_060625.2	Q96CQ1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A36	ENST00000324194.12 linkuse as main transcript	c.31T>C	p.Phe11Leu	missense_variant	1/7	1	NM_001104647.3	ENSP00000320688.6		Q96CQ1-1

Frequencies

GnomAD3 genomes

AF:

0.0000731

AC:

AN:

150426

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000857

AC:

AN:

116722

Hom.:

AF XY:

0.00

AC XY:

AN XY:

62248

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000233

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000819

AC:

108

AN:

1318424

Hom.:

Cov.:

AF XY:

0.0000906

AC XY:

AN XY:

651342

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000209

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.0000552

GnomAD4 genome

AF:

0.0000731

AC:

AN:

150544

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

73518

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000278

AC:

ESP6500EA

AF:

0.00

AC:

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

Nov 09, 2023

The c.31T>C (p.F11L) alteration is located in exon 1 (coding exon 1) of the SLC25A36 gene. This alteration results from a T to C substitution at nucleotide position 31, causing the phenylalanine (F) at amino acid position 11 to be replaced by a leucine (L). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.072

.;T;T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.84

T;T;T;D

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.41

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.52

N;.;N;.

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.63

N;N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.47

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.55

MutPred

0.35

Gain of glycosylation at T6 (P = 0.0484);Gain of glycosylation at T6 (P = 0.0484);Gain of glycosylation at T6 (P = 0.0484);Gain of glycosylation at T6 (P = 0.0484);

MVP

0.35

MPC

0.79

ClinPred

0.098

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.52

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