dbSNP rs371219132: SNX7:p.Thr115Lys (chr1-98685048-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015976.5(SNX7):c.344C>A(p.Thr115Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,382,540 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T115R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SNX7
NM_015976.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.16

Publications

0 publications found

Variant links:

Genes affected

SNX7 (HGNC:14971): (sorting nexin 7) 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, and its exact function is unknown. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Jun 2010]

SNX7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015976.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX7	NM_015976.5	MANE Select	c.344C>A	p.Thr115Lys	missense	Exon 2 of 9	NP_057060.2	Q9UNH6-3
SNX7	NM_152238.4		c.344C>A	p.Thr115Lys	missense	Exon 2 of 8	NP_689424.2	E9PNL2
SNX7	NM_001364903.1		c.152C>A	p.Thr51Lys	missense	Exon 3 of 10	NP_001351832.1	Q9UNH6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX7	ENST00000306121.8	TSL:1 MANE Select	c.344C>A	p.Thr115Lys	missense	Exon 2 of 9	ENSP00000304429.3	Q9UNH6-3
SNX7	ENST00000528824.1	TSL:1	n.*164C>A		non_coding_transcript_exon	Exon 3 of 9	ENSP00000435172.1	E9PLE1
SNX7	ENST00000528824.1	TSL:1	n.*164C>A		3_prime_UTR	Exon 3 of 9	ENSP00000435172.1	E9PLE1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1382540

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680328

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31378

American (AMR)

AF:

0.00

AC:

AN:

37108

Ashkenazi Jewish (ASJ)

AF:

0.0000423

AC:

AN:

23654

East Asian (EAS)

AF:

0.00

AC:

AN:

38256

South Asian (SAS)

AF:

0.00

AC:

AN:

71162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5462

European-Non Finnish (NFE)

AF:

9.37e-7

AC:

AN:

1067142

Other (OTH)

AF:

0.00

AC:

AN:

56854

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.70

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.85

PhyloP100

4.2

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.29

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.91

MutPred

0.54

Gain of methylation at T115 (P = 0.0209)

MVP

0.59

MPC

0.47

ClinPred

0.98

GERP RS

5.4

gMVP

0.73

Mutation Taster

=37/63

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over