chr1-98760071-G-C

Variant names:

• chr1-98760071-G-C
• rs2019213
• NM_015976.5:c.1296G>C

Variant summary

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

The NM_015976.5(SNX7):​c.1296G>C​(p.Glu432Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SNX7 NM_015976.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 18 publications found

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX7	NM_015976.5	MANE Select	c.1296G>C	p.Glu432Asp	missense	Exon 9 of 9	NP_057060.2
	SNX7	NM_152238.4		c.1131G>C	p.Glu377Asp	missense	Exon 8 of 8	NP_689424.2
	SNX7	NM_001364903.1		c.1104G>C	p.Glu368Asp	missense	Exon 10 of 10	NP_001351832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX7	ENST00000306121.8	TSL:1 MANE Select	c.1296G>C	p.Glu432Asp	missense	Exon 9 of 9	ENSP00000304429.3
	SNX7	ENST00000528824.1	TSL:1	n.*963G>C		non_coding_transcript_exon	Exon 9 of 9	ENSP00000435172.1
	SNX7	ENST00000528824.1	TSL:1	n.*963G>C		3_prime_UTR	Exon 9 of 9	ENSP00000435172.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.93	T
PhyloP100		0.0040
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.17
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.031	D
Polyphen		0.32	B
Vest4		0.69
MutPred		0.47		Loss of disorder (P = 0.2482)
MVP		0.43
MPC		0.35
ClinPred		0.94	D
GERP RS		-3.9
gMVP		0.37
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

dbSNP: rs2019213; hg19: chr1-99225627; COSMIC: COSV60265806;