15-64096055-G-C

Variant names:

• chr15-64096055-G-C
• NM_003099.5:c.42G>C
• SNX1 p.Leu14Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003099.5(SNX1):​c.42G>C​(p.Leu14Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX1 NM_003099.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-0.052 with no splicing effect.

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.42G>C	p.Leu14Leu	synonymous	Exon 1 of 15	NP_003090.2
	SNX1	NM_001242933.2		c.42G>C	p.Leu14Leu	synonymous	Exon 1 of 15	NP_001229862.1	Q13596-3
	SNX1	NM_148955.4		c.42G>C	p.Leu14Leu	synonymous	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.42G>C	p.Leu14Leu	synonymous	Exon 1 of 15	ENSP00000453785.1	Q13596-1
	SNX1	ENST00000561026.5	TSL:1	c.42G>C	p.Leu14Leu	synonymous	Exon 1 of 13	ENSP00000453567.1	Q13596-2
	SNX1	ENST00000380285.7	TSL:1	n.42G>C		non_coding_transcript_exon	Exon 1 of 15	ENSP00000369638.3	J3KPH4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.7
DANN	Benign	0.84
PhyloP100		-0.052
PromoterAI		-0.033	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-64388254;