chr7-26371803-CT-C

Variant names:

• chr7-26371803-CT-C
• rs201825204
• NM_013322.3:c.312-8delT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_013322.3(SNX10):​c.312-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,218,084 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: SNX10 NM_013322.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.492
• 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 0 ACMG points.

• PM2: Variant has high frequency in the AMR (0.0162) population. However there is too low homozygotes in high coverage region: (expected more than 45, got 0).
• BP6: Variant 7-26371803-CT-C is Benign according to our data. Variant chr7-26371803-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1991290.Status of the report is criteria_provided_single_submitter, 1 stars.

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.312-8delT		splice_region intron	N/A	NP_037454.2
	SNX10	NM_001318198.1		c.390-8delT		splice_region intron	N/A	NP_001305127.1	Q9Y5X0
	SNX10	NM_001362753.1		c.390-8delT		splice_region intron	N/A	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.312-8delT		splice_region intron	N/A	ENSP00000343709.5	Q9Y5X0-1
	SNX10	ENST00000396376.5	TSL:1	c.312-8delT		splice_region intron	N/A	ENSP00000379661.1	Q9Y5X0-1
	SNX10	ENST00000446848.6	TSL:1	c.312-8delT		splice_region intron	N/A	ENSP00000395474.3	Q9Y5X0-1

Frequencies

GnomAD3 genomes AF: 0.000162 AC: 24 AN: 148046 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000675

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.000921

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000135

Gnomad OTH AF: 0.000495

GnomAD2 exomes AF: 0.0165 AC: 2204 AN: 133662 AF XY: 0.0161

Gnomad AFR exome AF: 0.00722

Gnomad AMR exome AF: 0.0321

Gnomad ASJ exome AF: 0.0331

Gnomad EAS exome AF: 0.0159

Gnomad FIN exome AF: 0.0175

Gnomad NFE exome AF: 0.0117

Gnomad OTH exome AF: 0.0202

GnomAD4 exome AF: 0.0139 AC: 14916 AN: 1069956 Hom.: 0 Cov.: 22 AF XY: 0.0137 AC XY: 7283 AN XY: 531886

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

African (AFR) AF: 0.0138 AC: 333 AN: 24076

American (AMR) AF: 0.0174 AC: 548 AN: 31472

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 269 AN: 17972

East Asian (EAS) AF: 0.00919 AC: 263 AN: 28632

South Asian (SAS) AF: 0.0147 AC: 862 AN: 58596

European-Finnish (FIN) AF: 0.0104 AC: 413 AN: 39884

Middle Eastern (MID) AF: 0.00960 AC: 43 AN: 4478

European-Non Finnish (NFE) AF: 0.0141 AC: 11569 AN: 821212

Other (OTH) AF: 0.0141 AC: 616 AN: 43634

⚠️ 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 AF: 0.000162 AC: 24 AN: 148128 Hom.: 0 Cov.: 33 AF XY: 0.000208 AC XY: 15 AN XY: 72180

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

African (AFR) AF: 0.0000493 AC: 2 AN: 40604

American (AMR) AF: 0.0000674 AC: 1 AN: 14842

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3400

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5080

South Asian (SAS) AF: 0.00 AC: 0 AN: 4678

European-Finnish (FIN) AF: 0.000921 AC: 9 AN: 9768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000135 AC: 9 AN: 66522

Other (OTH) AF: 0.000490 AC: 1 AN: 2042

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0346 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201825204; hg19: chr7-26411423; COSMIC: COSV58400526; COSMIC: COSV58400526;