NM_013322.3:c.340G>A

Variant names:

• chr7-26371849-G-A
• rs1238426623
• NM_013322.3:c.340G>A

Variant summary

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

The NM_013322.3(SNX10):​c.340G>A​(p.Asp114Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNX10 NM_013322.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.60
• Publications: 0 publications found

Genes affected

SNX10 (HGNC:14974): (sorting nexin 10) 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. This gene may play a role in regulating endosome homeostasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

SNX10-AS1 (HGNC:55845): (SNX10 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013322.3. 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
	SNX10	NM_013322.3	MANE Select	c.340G>A	p.Asp114Asn	missense	Exon 6 of 7	NP_037454.2
	SNX10	NM_001318198.1		c.418G>A	p.Asp140Asn	missense	Exon 7 of 8	NP_001305127.1	Q9Y5X0
	SNX10	NM_001362753.1		c.418G>A	p.Asp140Asn	missense	Exon 8 of 9	NP_001349682.1	B4DJM0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX10	ENST00000338523.9	TSL:1 MANE Select	c.340G>A	p.Asp114Asn	missense	Exon 6 of 7	ENSP00000343709.5	Q9Y5X0-1
	SNX10	ENST00000396376.5	TSL:1	c.340G>A	p.Asp114Asn	missense	Exon 6 of 7	ENSP00000379661.1	Q9Y5X0-1
	SNX10	ENST00000446848.6	TSL:1	c.340G>A	p.Asp114Asn	missense	Exon 6 of 7	ENSP00000395474.3	Q9Y5X0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		8.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.39
Sift	Benign	0.098	T
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.57		Loss of solvent accessibility (P = 0.0169)
MVP		0.69
MPC		0.97
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.67
gMVP		0.49
Mutation Taster		=26/74	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1238426623; hg19: chr7-26411469;