chr7-26371828-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q107R) has been classified 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
• 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.319C>A	p.Gln107Lys	missense	Exon 6 of 7	NP_037454.2
	SNX10	NM_001318198.1		c.397C>A	p.Gln133Lys	missense	Exon 7 of 8	NP_001305127.1	Q9Y5X0
	SNX10	NM_001362753.1		c.397C>A	p.Gln133Lys	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.319C>A	p.Gln107Lys	missense	Exon 6 of 7	ENSP00000343709.5	Q9Y5X0-1
	SNX10	ENST00000396376.5	TSL:1	c.319C>A	p.Gln107Lys	missense	Exon 6 of 7	ENSP00000379661.1	Q9Y5X0-1
	SNX10	ENST00000446848.6	TSL:1	c.319C>A	p.Gln107Lys	missense	Exon 6 of 7	ENSP00000395474.3	Q9Y5X0-1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 86116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108302

Other (OTH) AF: 0.00 AC: 0 AN: 60234

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	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
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.12
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
Polyphen		0.88	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
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

hg19: chr7-26411448;