7-26371828-C-A

Variant names:

• chr7-26371828-C-A
• NM_013322.3:c.319C>A

Variant summary

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

The NM_013322.3(SNX10):​c.319C>A​(p.Gln107Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SNX10 NM_013322.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.80

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.319C>A	p.Gln107Lys	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.319C>A	p.Gln107Lys	missense_variant	Exon 6 of 7	1	NM_013322.3	ENSP00000343709.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457476 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725358

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jul 31, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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"). This variant has not been reported in the literature in individuals affected with SNX10-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 107 of the SNX10 protein (p.Gln107Lys). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.071	T;T;T;T;.;T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;.;.;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.40	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;L;L;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.1	.;N;N;N;N;.;D
REVEL	Benign	0.12
Sift	Benign	0.17	.;T;T;T;T;.;D
Sift4G	Benign	0.20	T;T;T;T;T;T;D
Polyphen		0.88	P;.;P;P;.;.;.
Vest4		0.41
MutPred		0.48		.;Gain of ubiquitination at Q133 (P = 0.0369);.;.;.;.;.;
MVP		0.55
MPC		0.66
ClinPred		0.83	D
GERP RS		5.8
Varity_R		0.58
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 22
DS_AL_spliceai		0.39		Position offset: -7

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: chr7-26411448;