chr1-98661847-C-T

Variant names:

• chr1-98661847-C-T
• NM_015976.5:c.116C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 14/21 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
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX7	NM_015976.5	MANE Select	c.116C>T	p.Ala39Val	missense	Exon 1 of 9	NP_057060.2	Q9UNH6-3
	SNX7	NM_152238.4		c.116C>T	p.Ala39Val	missense	Exon 1 of 8	NP_689424.2	E9PNL2
	SNX7	NM_001364903.1		c.-197C>T		5_prime_UTR	Exon 1 of 10	NP_001351832.1	Q9UNH6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX7	ENST00000306121.8	TSL:1 MANE Select	c.116C>T	p.Ala39Val	missense	Exon 1 of 9	ENSP00000304429.3	Q9UNH6-3
	SNX7	ENST00000971618.1		c.116C>T	p.Ala39Val	missense	Exon 1 of 9	ENSP00000641677.1
	SNX7	ENST00000851356.1		c.116C>T	p.Ala39Val	missense	Exon 1 of 9	ENSP00000521415.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
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
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-0.35
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.0080
Sift	Benign	1.0	T
Sift4G	Benign	0.085	T
Polyphen		0.0	B
Vest4		0.026
MutPred		0.34		Loss of helix (P = 0.0138)
MVP		0.12
MPC		0.088
ClinPred		0.069	T
GERP RS		0.35
PromoterAI		-0.087	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.16
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

hg19: chr1-99127403;