Variant 5-110746313-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_138773.4(SLC25A46):c.429C>T(p.Val143Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00984 in 1,592,252 control chromosomes in the GnomAD database, including 402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 194 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 208 hom. )

Consequence

SLC25A46
NM_138773.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.329

Variant links:

Genes affected

SLC25A46 (HGNC:25198): (solute carrier family 25 member 46) This gene encodes a mitochondrial solute carrier protein family member. It functions in promoting mitochondrial fission, and prevents the formation of hyperfilamentous mitochondria. Mutation of this gene results in neuropathy and optic atrophy. [provided by RefSeq, Aug 2016]

SLC25A46 links:

SLC25A46 (HGNC:):

SLC25A46 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 5-110746313-C-T is Benign according to our data. Variant chr5-110746313-C-T is described in ClinVar as [Benign]. Clinvar id is 475796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-110746313-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.329 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A46	NM_138773.4 linkuse as main transcript	c.429C>T	p.Val143Val	synonymous_variant	4/8	ENST00000355943.8	NP_620128.1	Q96AG3-1
SLC25A46	NM_001303249.3 linkuse as main transcript	c.429C>T	p.Val143Val	synonymous_variant	4/8		NP_001290178.1	Q96AG3-3
SLC25A46	NM_001303250.3 linkuse as main transcript	c.156C>T	p.Val52Val	synonymous_variant	4/8		NP_001290179.1	Q96AG3B4DY98
SLC25A46	NR_138151.2 linkuse as main transcript	n.542C>T		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A46	ENST00000355943.8 linkuse as main transcript	c.429C>T	p.Val143Val	synonymous_variant	4/8	1	NM_138773.4	ENSP00000348211.3		Q96AG3-1

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4606

AN:

152086

Hom.:

193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0939

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00685

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.00973

AC:

2238

AN:

229912

Hom.:

AF XY:

0.00812

AC XY:

1015

AN XY:

125030

show subpopulations

Gnomad AFR exome

AF:

0.0893

Gnomad AMR exome

AF:

0.00604

Gnomad ASJ exome

AF:

0.00104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000636

Gnomad FIN exome

AF:

0.00108

Gnomad NFE exome

AF:

0.00658

Gnomad OTH exome

AF:

0.00797

GnomAD4 exome

AF:

0.00768

AC:

11059

AN:

1440050

Hom.:

208

Cov.:

AF XY:

0.00722

AC XY:

5172

AN XY:

716524

show subpopulations

Gnomad4 AFR exome

AF:

0.0960

Gnomad4 AMR exome

AF:

0.00728

Gnomad4 ASJ exome

AF:

0.00113

Gnomad4 EAS exome

AF:

0.0000263

Gnomad4 SAS exome

AF:

0.000873

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.00620

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.0303

AC:

4613

AN:

152202

Hom.:

194

Cov.:

AF XY:

0.0288

AC XY:

2141

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0939

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00682

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0164

Hom.:

Bravo

AF:

0.0352

Asia WGS

AF:

0.00608

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neuropathy, hereditary motor and sensory, type 6B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

9.2

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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