NM_015976.5:c.296C>T

Variant names:

• chr1-98685000-C-T
• rs187349988
• NM_015976.5:c.296C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015976.5(SNX7):​c.296C>T​(p.Thr99Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T99R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX7 NM_015976.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX7	NM_015976.5	c.296C>T	p.Thr99Ile	missense_variant	Exon 2 of 9	ENST00000306121.8	NP_057060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX7	ENST00000306121.8	c.296C>T	p.Thr99Ile	missense_variant	Exon 2 of 9	1	NM_015976.5	ENSP00000304429.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Benign	0.20
Sift	Benign	0.080	T;T;T
Sift4G	Uncertain	0.0080	D;T;T
Polyphen		1.0	D;P;.
Vest4		0.62
MutPred		0.57		Loss of disorder (P = 0.0702);Loss of disorder (P = 0.0702);.;
MVP		0.52
MPC		0.15
ClinPred		0.94	D
GERP RS		5.4
gMVP		0.56

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

LitVar

Other links and lift over

dbSNP: rs187349988; hg19: chr1-99150556;