Genetic Variant NM_006358.4:c.592A>T (chr22-40777233-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_006358.4(SLC25A17):c.592A>T(p.Met198Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,670 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. 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. M198V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC25A17
NM_006358.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380

Publications

1 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:

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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=0.10769731).

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.592A>T	p.Met198Leu	missense	Exon 6 of 9	NP_006349.1	O43808
SLC25A17	NM_001282726.2		c.481A>T	p.Met161Leu	missense	Exon 7 of 10	NP_001269655.1	B4DU97
SLC25A17	NM_001282727.2		c.373A>T	p.Met125Leu	missense	Exon 4 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.592A>T	p.Met198Leu	missense	Exon 6 of 9	ENSP00000390722.2	O43808
SLC25A17	ENST00000263255.10	TSL:1	n.*248A>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000263255.6	F8WA85
SLC25A17	ENST00000491545.5	TSL:1	n.994A>T		non_coding_transcript_exon	Exon 8 of 11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111836

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.9

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.021

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.69

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.20

PhyloP100

0.038

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.67

REVEL

Benign

0.24

Sift

Benign

0.31

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.26

MutPred

0.32

Gain of relative solvent accessibility (P = 0.0249)

MVP

0.54

MPC

0.16

ClinPred

0.17

GERP RS

4.8

Varity_R

0.13

gMVP

0.41

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over