Genetic Variant NM_015976.5:c.344C>A (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:

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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

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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