Genetic Variant NM_006358.4:c.908G>A (chr22-40770850-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006358.4(SLC25A17):c.908G>A(p.Arg303His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,610,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SLC25A17
NM_006358.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.348

Publications

0 publications found

Variant links:

Genes affected

SLC25A17 (HGNC:10987): (solute carrier family 25 member 17) This gene encodes a peroxisomal membrane protein that belongs to the family of mitochondrial solute carriers. It is expressed in the liver, and is likely involved in transport. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

SLC25A17 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022931963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006358.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A17	NM_006358.4	MANE Select	c.908G>A	p.Arg303His	missense	Exon 9 of 9	NP_006349.1	O43808
SLC25A17	NM_001282726.2		c.797G>A	p.Arg266His	missense	Exon 10 of 10	NP_001269655.1	B4DU97
SLC25A17	NM_001282727.2		c.689G>A	p.Arg230His	missense	Exon 7 of 7	NP_001269656.1	F6RTR7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A17	ENST00000435456.7	TSL:1 MANE Select	c.908G>A	p.Arg303His	missense	Exon 9 of 9	ENSP00000390722.2	O43808
SLC25A17	ENST00000263255.10	TSL:1	n.*564G>A		non_coding_transcript_exon	Exon 8 of 8	ENSP00000263255.6	F8WA85
SLC25A17	ENST00000491545.5	TSL:1	n.1310G>A		non_coding_transcript_exon	Exon 11 of 11

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

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

GnomAD2 exomes

AF:

0.0000720

AC:

AN:

249980

AF XY:

0.0000592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000548

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1458076

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725410

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33382

American (AMR)

AF:

0.000135

AC:

AN:

44414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.000152

AC:

AN:

39592

South Asian (SAS)

AF:

0.0000466

AC:

AN:

85808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1109622

Other (OTH)

AF:

0.0000166

AC:

AN:

60162

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

AF:

0.0000197

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.2

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.037

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.58

M_CAP

Benign

0.040

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.81

PhyloP100

0.35

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.5

REVEL

Benign

0.17

Sift

Benign

0.19

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.028

MutPred

0.36

Loss of MoRF binding (P = 0.0027)

MVP

0.74

MPC

0.21

ClinPred

0.034

GERP RS

-0.19

Varity_R

0.023

gMVP

0.36

Mutation Taster

=92/8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over