7-26360980-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_013322.3(SNX10):c.30T>G(p.Phe10Leu) variant causes a missense change involving the alteration of a non-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: 0.0430

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]

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 6 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/exons	MANE	UniProt
SNX10	NM_013322.3	c.30T>G	p.Phe10Leu	missense_variant	3/7	ENST00000338523.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX10	ENST00000338523.9	c.30T>G	p.Phe10Leu	missense_variant	3/7	1	NM_013322.3	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Mar 15, 2022

This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 10 of the SNX10 protein (p.Phe10Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SNX10-related conditions. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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	0.95
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;T;.;T;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.57	T;T;.;T;.;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.50	D;D;D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.7	M;.;M;.;M;.
MutationTaster	Benign	0.97	D;D;D;D
PrimateAI	Pathogenic	0.87	D
REVEL	Benign	0.23
Sift4G	Benign	0.20	T;T;T;D;T;T
Polyphen		0.89	P;.;P;.;P;.
Vest4		0.49
MutPred		0.53		.;Gain of MoRF binding (P = 0.1286);.;Gain of MoRF binding (P = 0.1286);.;.;
MVP		0.44
MPC		0.87
ClinPred		0.98	D
GERP RS		-0.86
Varity_R		0.45
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr7-26400600;