15-64096053-C-G

Variant names:

• chr15-64096053-C-G
• rs370223175
• NM_003099.5:c.40C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003099.5(SNX1):​c.40C>G​(p.Leu14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SNX1 NM_003099.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.828
• Publications: 0 publications found

Genes affected

SNX1 (HGNC:11172): (sorting nexin 1) 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 endosomal protein regulates the cell-surface expression of epidermal growth factor receptor. This protein also has a role in sorting protease-activated receptor-1 from early endosomes to lysosomes. This protein may form oligomeric complexes with family members. This gene results in three transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16923687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003099.5. 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
	SNX1	NM_003099.5	MANE Select	c.40C>G	p.Leu14Val	missense	Exon 1 of 15	NP_003090.2
	SNX1	NM_001242933.2		c.40C>G	p.Leu14Val	missense	Exon 1 of 15	NP_001229862.1	Q13596-3
	SNX1	NM_148955.4		c.40C>G	p.Leu14Val	missense	Exon 1 of 13	NP_683758.1	Q13596-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX1	ENST00000559844.6	TSL:1 MANE Select	c.40C>G	p.Leu14Val	missense	Exon 1 of 15	ENSP00000453785.1	Q13596-1
	SNX1	ENST00000561026.5	TSL:1	c.40C>G	p.Leu14Val	missense	Exon 1 of 13	ENSP00000453567.1	Q13596-2
	SNX1	ENST00000380285.7	TSL:1	n.40C>G		non_coding_transcript_exon	Exon 1 of 15	ENSP00000369638.3	J3KPH4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 208966 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438990 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 714464

African (AFR) AF: 0.00 AC: 0 AN: 33350

American (AMR) AF: 0.00 AC: 0 AN: 40722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25642

East Asian (EAS) AF: 0.00 AC: 0 AN: 38916

South Asian (SAS) AF: 0.00 AC: 0 AN: 83406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104758

Other (OTH) AF: 0.00 AC: 0 AN: 59682

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.076
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.0051
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.83
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.030
Sift	Benign	0.21	T
Sift4G	Benign	0.17	T
Polyphen		0.70	P
Vest4		0.45
MutPred		0.46		Loss of catalytic residue at L14 (P = 0.0905)
MVP		0.39
MPC		0.25
ClinPred		0.41	T
GERP RS		3.6
PromoterAI		0.00020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.17
Mutation Taster		=92/8	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

dbSNP: rs370223175; hg19: chr15-64388252;