chr22-40777314-G-A

Variant names:

• chr22-40777314-G-A
• NM_006358.4:c.511C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006358.4(SLC25A17):​c.511C>T​(p.Pro171Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A17 NM_006358.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.86
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.891

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.511C>T	p.Pro171Ser	missense	Exon 6 of 9	NP_006349.1	O43808
	SLC25A17	NM_001282726.2		c.400C>T	p.Pro134Ser	missense	Exon 7 of 10	NP_001269655.1	B4DU97
	SLC25A17	NM_001282727.2		c.292C>T	p.Pro98Ser	missense	Exon 4 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.511C>T	p.Pro171Ser	missense	Exon 6 of 9	ENSP00000390722.2	O43808
	SLC25A17	ENST00000263255.10	TSL:1	n.*167C>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000263255.6	F8WA85
	SLC25A17	ENST00000491545.5	TSL:1	n.913C>T		non_coding_transcript_exon	Exon 8 of 11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.9	L
PhyloP100		9.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.63
Sift	Benign	0.034	D
Sift4G	Uncertain	0.058	T
Polyphen		0.89	P
Vest4		0.90
MutPred		0.70		Gain of catalytic residue at P171 (P = 0.0223)
MVP		0.96
MPC		0.53
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.61
gMVP		0.93
Mutation Taster		=42/58	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

Other links and lift over

hg19: chr22-41173318; COSMIC: COSV104550881; COSMIC: COSV104550881;