7-26371915-G-T

Variant names:

• chr7-26371915-G-T
• NM_013322.3:c.406G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013322.3(SNX10):​c.406G>T​(p.Gly136Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 8.55

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX10	NM_013322.3	c.406G>T	p.Gly136Trp	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.406G>T	p.Gly136Trp	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

Dec 26, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T;T;T;.;T;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;.;.;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.022	D
MutationAssessor	Pathogenic	3.0	M;.;M;M;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-7.0	.;D;D;D;D;.;D
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	.;D;D;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0	D;.;D;D;.;.;.
Vest4		0.68
MutPred		0.55		.;Gain of solvent accessibility (P = 0.0062);.;.;.;.;.;
MVP		0.77
MPC		1.1
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: 6

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: chr7-26411535;