1-98661847-C-T

Position:

• chr1-98661847-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015976.5(SNX7):​c.116C>T​(p.Ala39Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX7 NM_015976.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.355

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03549996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX7	NM_015976.5	c.116C>T	p.Ala39Val	missense_variant	1/9	ENST00000306121.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX7	ENST00000306121.8	c.116C>T	p.Ala39Val	missense_variant	1/9	1	NM_015976.5	P1
SNX7	ENST00000529992.5	c.116C>T	p.Ala39Val	missense_variant	1/8	2
SNX7	ENST00000473868.5	n.38C>T		non_coding_transcript_exon_variant	1/3	3
SNX7	ENST00000528824.1			upstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.116C>T (p.A39V) alteration is located in exon 1 (coding exon 1) of the SNX7 gene. This alteration results from a C to T substitution at nucleotide position 116, causing the alanine (A) at amino acid position 39 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0078	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.69	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.15	N;N
REVEL	Benign	0.0080
Sift	Benign	1.0	T;T
Sift4G	Benign	0.085	T;T
Polyphen		0.0	B;B
Vest4		0.026
MutPred		0.34		Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);
MVP		0.12
MPC		0.088
ClinPred		0.069	T
GERP RS		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-99127403;