Variant chr3-140973967-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001104647.3(SLC25A36):c.704C>T(p.Thr235Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,585,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SLC25A36
NM_001104647.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A36	NM_001104647.3 linkuse as main transcript	c.704C>T	p.Thr235Ile	missense_variant	6/7	ENST00000324194.12	NP_001098117.1	Q96CQ1-1A0A384MEA9
SLC25A36	NM_018155.3 linkuse as main transcript	c.704C>T	p.Thr235Ile	missense_variant	6/7		NP_060625.2	Q96CQ1-3
SLC25A36	XM_047448440.1 linkuse as main transcript	c.800C>T	p.Thr267Ile	missense_variant	6/7		XP_047304396.1
SLC25A36	XM_005247575.6 linkuse as main transcript	c.335C>T	p.Thr112Ile	missense_variant	4/5		XP_005247632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A36	ENST00000324194.12 linkuse as main transcript	c.704C>T	p.Thr235Ile	missense_variant	6/7	1	NM_001104647.3	ENSP00000320688.6		Q96CQ1-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

242016

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131000

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:

0.00000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000160

AC:

AN:

1433686

Hom.:

Cov.:

AF XY:

0.00000843

AC XY:

AN XY:

711814

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

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:

0.00

Gnomad4 NFE exome

AF:

0.0000201

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Mar 28, 2022

The c.704C>T (p.T235I) alteration is located in exon 6 (coding exon 6) of the SLC25A36 gene. This alteration results from a C to T substitution at nucleotide position 704, causing the threonine (T) at amino acid position 235 to be replaced by an isoleucine (I). 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

0.17

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

DANN

Benign

0.82

DEOGEN2

Benign

0.10

.;T;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

-0.030

N;N;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.43

N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.89

T;T;T

Sift4G

Benign

0.80

T;T;T

Polyphen

0.0060

B;D;.

Vest4

0.87

MutPred

0.43

Loss of glycosylation at S236 (P = 0.0387);Loss of glycosylation at S236 (P = 0.0387);.;

MVP

0.39

MPC

0.83

ClinPred

0.33

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.95

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