22-40773980-C-T

Variant names:

• chr22-40773980-C-T
• rs200817852
• NM_006358.4:c.733G>A

Variant summary

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

The NM_006358.4(SLC25A17):​c.733G>A​(p.Gly245Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00015 in 1,613,362 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: SLC25A17 NM_006358.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16
• Publications: 1 publications found

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]

ACMG classification

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A17	NM_006358.4	MANE Select	c.733G>A	p.Gly245Arg	missense	Exon 8 of 9	NP_006349.1	O43808
	SLC25A17	NM_001282726.2		c.622G>A	p.Gly208Arg	missense	Exon 9 of 10	NP_001269655.1	B4DU97
	SLC25A17	NM_001282727.2		c.514G>A	p.Gly172Arg	missense	Exon 6 of 7	NP_001269656.1	F6RTR7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A17	ENST00000435456.7	TSL:1 MANE Select	c.733G>A	p.Gly245Arg	missense	Exon 8 of 9	ENSP00000390722.2	O43808
	SLC25A17	ENST00000263255.10	TSL:1	n.*389G>A		non_coding_transcript_exon	Exon 7 of 8	ENSP00000263255.6	F8WA85
	SLC25A17	ENST00000491545.5	TSL:1	n.1135G>A		non_coding_transcript_exon	Exon 10 of 11

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000636 AC: 16 AN: 251468 AF XY: 0.0000736

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: 0.000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000156 AC: 228 AN: 1461278 Hom.: 0 Cov.: 29 AF XY: 0.000149 AC XY: 108 AN XY: 727028

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000197 AC: 219 AN: 1111470

Other (OTH) AF: 0.000116 AC: 7 AN: 60378

GnomAD4 genome AF: 0.0000921 AC: 14 AN: 152084 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74266

African (AFR) AF: 0.0000483 AC: 2 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000122 Hom.: 0

Bravo AF: 0.0000945

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
PhyloP100		6.2
Varity_R		0.22
gMVP		0.74
Mutation Taster		=45/55	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs200817852; hg19: chr22-41169984;