7-26371849-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 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

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a domain PX (size 117) in uniprot entity SNX10_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_013322.3
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX10	NM_013322.3	c.340G>A	p.Asp114Asn	missense_variant	Exon 6 of 7	ENST00000338523.9	NP_037454.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX10	ENST00000338523.9	c.340G>A	p.Asp114Asn	missense_variant	Exon 6 of 7	1	NM_013322.3	ENSP00000343709.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 10, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces aspartic acid with asparagine at codon 114 of the SNX10 protein (p.Asp114Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SNX10-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

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;T;T;T;.;T;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;.;.;D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.6	M;.;M;M;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.2	.;D;D;D;D;.;D
REVEL	Uncertain	0.39
Sift	Benign	0.098	.;T;T;T;T;.;T
Sift4G	Uncertain	0.016	D;D;D;D;D;D;D
Polyphen		1.0	D;.;D;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-26411469;