rs758140632

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138773.4(SLC25A46):c.196G>A(p.Val66Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000353 in 1,416,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V66L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

SLC25A46
NM_138773.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.21

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

neuropathy, hereditary motor and sensory, type 6B
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
pontocerebellar hypoplasia, type 1E
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hereditary motor and sensory neuropathy type 6
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
pontocerebellar hypoplasia type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SLC25A46 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.187673).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC25A46	NM_138773.4	MANE Select	c.196G>A	p.Val66Met	missense	Exon 1 of 8	NP_620128.1
SLC25A46	NM_001303249.3		c.196G>A	p.Val66Met	missense	Exon 1 of 8	NP_001290178.1
SLC25A46	NR_138151.2		n.309G>A		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC25A46	ENST00000355943.8	TSL:1 MANE Select	c.196G>A	p.Val66Met	missense	Exon 1 of 8	ENSP00000348211.3
SLC25A46	ENST00000447245.6	TSL:2	c.196G>A	p.Val66Met	missense	Exon 1 of 8	ENSP00000399717.2
SLC25A46	ENST00000513807.5	TSL:2	c.-204+1068G>A		intron	N/A	ENSP00000421134.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000571

AC:

AN:

175202

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000353

AC:

AN:

1416874

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

700704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32658

American (AMR)

AF:

0.00

AC:

AN:

37830

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25354

East Asian (EAS)

AF:

0.0000266

AC:

AN:

37550

South Asian (SAS)

AF:

0.0000372

AC:

AN:

80710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

9.18e-7

AC:

AN:

1089466

Other (OTH)

AF:

0.00

AC:

AN:

58708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000842

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.90

PhyloP100

3.2

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.55

REVEL

Benign

0.20

Sift

Benign

0.095

Sift4G

Benign

0.12

Polyphen

0.30

Vest4

0.11

MutPred

0.072

Loss of catalytic residue at V66 (P = 0.0261)

MVP

0.69

MPC

0.094

ClinPred

0.53

GERP RS

3.2

PromoterAI

-0.025

Neutral

(source)

Varity_R

0.085

gMVP

0.27

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over