Variant chr5-110739354-G-C 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_138773.4(SLC25A46):c.235G>C(p.Glu79Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000128 in 1,561,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E79K) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SLC25A46
NM_138773.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.64

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 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=0.20985958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC25A46	NM_138773.4 linkuse as main transcript	c.235G>C	p.Glu79Gln	missense_variant	1/8	ENST00000355943.8
SLC25A46	NM_001303249.3 linkuse as main transcript	c.235G>C	p.Glu79Gln	missense_variant	1/8
SLC25A46	NM_001303250.3 linkuse as main transcript	c.10+1107G>C		intron_variant
SLC25A46	NR_138151.2 linkuse as main transcript	n.348G>C		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A46	ENST00000355943.8 linkuse as main transcript	c.235G>C	p.Glu79Gln	missense_variant	1/8	1	NM_138773.4	P1	Q96AG3-1
SLC25A46	ENST00000447245.6 linkuse as main transcript	c.235G>C	p.Glu79Gln	missense_variant	1/8	2			Q96AG3-3
SLC25A46	ENST00000513807.5 linkuse as main transcript	c.-204+1107G>C		intron_variant		2
SLC25A46	ENST00000508781.5 linkuse as main transcript	n.112+1107G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.09e-7

AC:

AN:

1409962

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697136

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151912

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.235G>C (p.E79Q) alteration is located in exon 1 (coding exon 1) of the SLC25A46 gene. This alteration results from a G to C substitution at nucleotide position 235, causing the glutamic acid (E) at amino acid position 79 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0063

T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.70

T;T

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.39

N;N

REVEL

Benign

0.22

Sift

Benign

0.14

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.019

B;.

Vest4

0.34

MutPred

0.10

Loss of phosphorylation at S82 (P = 0.1641);Loss of phosphorylation at S82 (P = 0.1641);

MVP

0.62

MPC

0.066

ClinPred

0.27

GERP RS

3.1

Varity_R

0.15

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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