Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_138773.4(SLC25A46):c.46G>T(p.Gly16Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000429 in 1,397,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G16G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

SLC25A46
NM_138773.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

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 links:

TMEM232 (HGNC:37270): (transmembrane protein 232) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM232 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.805

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.46G>T	p.Gly16Cys	missense	Exon 1 of 8	NP_620128.1
SLC25A46	NM_001303249.3		c.46G>T	p.Gly16Cys	missense	Exon 1 of 8	NP_001290178.1
SLC25A46	NR_138151.2		n.159G>T		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.46G>T	p.Gly16Cys	missense	Exon 1 of 8	ENSP00000348211.3
SLC25A46	ENST00000447245.6	TSL:2	c.46G>T	p.Gly16Cys	missense	Exon 1 of 8	ENSP00000399717.2
SLC25A46	ENST00000513807.5	TSL:2	c.-204+918G>T		intron	N/A	ENSP00000421134.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

153306

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000429

AC:

AN:

1397968

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689604

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31618

American (AMR)

AF:

0.00

AC:

AN:

35716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25160

East Asian (EAS)

AF:

0.00

AC:

AN:

35788

South Asian (SAS)

AF:

0.00

AC:

AN:

79224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5402

European-Non Finnish (NFE)

AF:

0.00000556

AC:

AN:

1079030

Other (OTH)

AF:

0.00

AC:

AN:

57966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.0000104

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neuropathy, hereditary motor and sensory, type 6B (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.83

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

0.49

MutationAssessor

Benign

1.9

PhyloP100

4.9

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.61

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.87

Vest4

0.57

MutPred

0.51

Loss of disorder (P = 0.0301)

MVP

0.84

MPC

0.27

ClinPred

0.98

GERP RS

4.0

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.62

gMVP

0.57

Mutation Taster

=62/38

polymorphism

(source)

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

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

rs770562376

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over