Variant rs151055603 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_138773.4(SLC25A46):c.378A>G(p.Gln126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,605,066 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 33 hom. )

Consequence

SLC25A46
NM_138773.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.351

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 5-110743781-A-G is Benign according to our data. Variant chr5-110743781-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 475793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-110743781-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.351 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00412 (627/152264) while in subpopulation NFE AF= 0.00563 (383/67972). AF 95% confidence interval is 0.00517. There are 3 homozygotes in gnomad4. There are 311 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC25A46	NM_138773.4 linkuse as main transcript	c.378A>G	p.Gln126=	synonymous_variant	3/8	ENST00000355943.8	NP_620128.1
SLC25A46	NM_001303249.3 linkuse as main transcript	c.378A>G	p.Gln126=	synonymous_variant	3/8		NP_001290178.1
SLC25A46	NM_001303250.3 linkuse as main transcript	c.105A>G	p.Gln35=	synonymous_variant	3/8		NP_001290179.1
SLC25A46	NR_138151.2 linkuse as main transcript	n.491A>G		non_coding_transcript_exon_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A46	ENST00000355943.8 linkuse as main transcript	c.378A>G	p.Gln126=	synonymous_variant	3/8	1	NM_138773.4	ENSP00000348211	P1	Q96AG3-1

Frequencies

GnomAD3 genomes

AF:

0.00412

AC:

627

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00800

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00563

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00448

AC:

1112

AN:

248170

Hom.:

AF XY:

0.00486

AC XY:

652

AN XY:

134286

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.000220

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.00825

Gnomad NFE exome

AF:

0.00606

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.00544

AC:

7906

AN:

1452802

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

3759

AN XY:

723012

show subpopulations

Gnomad4 AFR exome

AF:

0.000632

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.00152

Gnomad4 FIN exome

AF:

0.00833

Gnomad4 NFE exome

AF:

0.00602

Gnomad4 OTH exome

AF:

0.00504

GnomAD4 genome

AF:

0.00412

AC:

627

AN:

152264

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

311

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00800

Gnomad4 NFE

AF:

0.00563

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00400

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	SLC25A46: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Neuropathy, hereditary motor and sensory, type 6B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.3

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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