1-98760071-G-T

Variant names:

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

Variant summary

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

The NM_015976.5(SNX7):​c.1296G>T​(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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX7	NM_015976.5	c.1296G>T	p.Glu432Asp	missense_variant	Exon 9 of 9	ENST00000306121.8	NP_057060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX7	ENST00000306121.8	c.1296G>T	p.Glu432Asp	missense_variant	Exon 9 of 9	1	NM_015976.5	ENSP00000304429.3
SNX7	ENST00000528824.1	n.*963G>T		non_coding_transcript_exon_variant	Exon 9 of 9	1		ENSP00000435172.1
SNX7	ENST00000528824.1	n.*963G>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000435172.1
SNX7	ENST00000529992.5	c.1131G>T	p.Glu377Asp	missense_variant	Exon 8 of 8	2		ENSP00000434731.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1454098 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 723876

African (AFR) AF: 0.00 AC: 0 AN: 33232

American (AMR) AF: 0.00 AC: 0 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105312

Other (OTH) AF: 0.00 AC: 0 AN: 60124

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 240377

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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	0.57	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	.;.
PhyloP100		0.0040
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.031	D;D
Vest4		0.69
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)		0.10		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;