Genetic Variant SNX17:p.Gln106His (chr2-27373308-A-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_014748.4(SNX17):c.318A>C(p.Gln106His) 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 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q106Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SNX17
NM_014748.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.457

Publications

0 publications found

Variant links:

Genes affected

SNX17 (HGNC:14979): (sorting nexin 17) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like some family members, but contains a B41 domain. This protein interacts with the cytoplasmic domain of P-selectin, and may function in the intracellular trafficking of P-selectin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]

SNX17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.795

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014748.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX17	NM_014748.4	MANE Select	c.318A>C	p.Gln106His	missense	Exon 4 of 15	NP_055563.1	Q15036-1
SNX17	NM_001267059.2		c.282A>C	p.Gln94His	missense	Exon 4 of 15	NP_001253988.1	B4DTB8
SNX17	NM_001267061.2		c.258A>C	p.Gln86His	missense	Exon 4 of 15	NP_001253990.1	B4DQ37

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX17	ENST00000233575.7	TSL:1 MANE Select	c.318A>C	p.Gln106His	missense	Exon 4 of 15	ENSP00000233575.2	Q15036-1
SNX17	ENST00000440760.5	TSL:1	n.*163A>C		non_coding_transcript_exon	Exon 3 of 14	ENSP00000399727.1	F8WFA0
SNX17	ENST00000453453.1	TSL:1	n.125A>C		non_coding_transcript_exon	Exon 2 of 12	ENSP00000401922.1	F8WEG6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111984

Other (OTH)

AF:

0.00

AC:

AN:

60396

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Uncertain

0.48

Eigen

Benign

0.045

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.079

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.66

MutationAssessor

Pathogenic

3.0

PhyloP100

0.46

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.36

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.95

Vest4

0.79

MutPred

0.49

Gain of catalytic residue at R104 (P = 0.0633)

MVP

0.73

MPC

0.65

ClinPred

0.99

GERP RS

-1.6

Varity_R

0.94

gMVP

0.59

Mutation Taster

=15/85

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over