NM_014426.4:c.794A>G

Variant names:

• chr20-17949101-T-C
• NM_014426.4:c.794A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014426.4(SNX5):​c.794A>G​(p.Tyr265Cys) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNX5 NM_014426.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• Publications: 0 publications found

Genes affected

SNX5 (HGNC:14969): (sorting nexin 5) 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 functions in endosomal sorting, the phosphoinositide-signaling pathway, and macropinocytosis. This gene may play a role in the tumorigenesis of papillary thyroid carcinoma. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40214306).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014426.4. 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
	SNX5	NM_014426.4	MANE Select	c.794A>G	p.Tyr265Cys	missense splice_region	Exon 9 of 13	NP_055241.1	Q9Y5X3-1
	SNX5	NM_152227.3		c.794A>G	p.Tyr265Cys	missense splice_region	Exon 10 of 14	NP_689413.1	Q9Y5X3-1
	SNX5	NM_001282454.2		c.479A>G	p.Tyr160Cys	missense splice_region	Exon 9 of 13	NP_001269383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX5	ENST00000377759.9	TSL:1 MANE Select	c.794A>G	p.Tyr265Cys	missense splice_region	Exon 9 of 13	ENSP00000366988.3	Q9Y5X3-1
	SNX5	ENST00000377768.7	TSL:1	c.794A>G	p.Tyr265Cys	missense splice_region	Exon 10 of 14	ENSP00000366998.3	Q9Y5X3-1
	SNX5	ENST00000490175.5	TSL:1	n.844A>G		splice_region non_coding_transcript_exon	Exon 9 of 13

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.18
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.044
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.16
Sift	Benign	0.17	T
Sift4G	Benign	0.070	T
Polyphen		0.024	B
Vest4		0.57
MutPred		0.52		Gain of methylation at K264 (P = 0.0125)
MVP		0.63
MPC		0.42
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.77
gMVP		0.36
Mutation Taster		=35/65	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr20-17929745;