Variant chr3-140963173-G-A 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.331G>A(p.Asp111Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000313 in 1,596,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SLC25A36
NM_001104647.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.15

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07416165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A36	NM_001104647.3 linkuse as main transcript	c.331G>A	p.Asp111Asn	missense_variant	4/7	ENST00000324194.12	NP_001098117.1	Q96CQ1-1A0A384MEA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A36	ENST00000324194.12 linkuse as main transcript	c.331G>A	p.Asp111Asn	missense_variant	4/7	1	NM_001104647.3	ENSP00000320688.6		Q96CQ1-1

Frequencies

GnomAD3 genomes

AF:

0.0000792

AC:

AN:

151522

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000591

AC:

AN:

236920

Hom.:

AF XY:

0.0000466

AC XY:

AN XY:

128702

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.000231

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:

0.0000453

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000263

AC:

AN:

1444566

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

718512

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.000223

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000199

Gnomad4 OTH exome

AF:

0.0000503

GnomAD4 genome

AF:

0.0000792

AC:

AN:

151522

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

73948

show subpopulations

Gnomad4 AFR

AF:

0.000242

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000903

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000494

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 11, 2024

The c.331G>A (p.D111N) alteration is located in exon 4 (coding exon 4) of the SLC25A36 gene. This alteration results from a G to A substitution at nucleotide position 331, causing the aspartic acid (D) at amino acid position 111 to be replaced by an asparagine (N). 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

0.077

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

.;T;T;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.072

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.76

T;T;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.074

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.38

N;.;N;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

0.65

N;N;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.45

T;T;T;T;T

Sift4G

Benign

0.77

T;T;T;T;T

Polyphen

0.0

B;B;B;.;.

Vest4

0.17

MVP

0.17

MPC

0.66

ClinPred

0.042

GERP RS

4.3

Varity_R

0.075

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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