7-26371803-CTT-CTTT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_013322.3(SNX10):​c.312-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,285,996 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 0.00076 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (0 hom.)
• Consequence: SNX10 NM_013322.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Variant has high frequency in the EAS (0.00825) population. However there is too low homozygotes in high coverage region: (expected more than 4, got 0).
• BP6: Variant 7-26371803-C-CT is Benign according to our data. Variant chr7-26371803-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1533579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000755 (112/148266) while in subpopulation EAS AF = 0.00335 (17/5080). AF 95% confidence interval is 0.00213. There are 0 homozygotes in GnomAd4. There are 51 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 111 AN: 148184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00334

Gnomad SAS AF: 0.000639

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000255

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00393 AC: 525 AN: 133662 AF XY: 0.00354

Gnomad AFR exome AF: 0.00376

Gnomad AMR exome AF: 0.00748

Gnomad ASJ exome AF: 0.00411

Gnomad EAS exome AF: 0.00673

Gnomad FIN exome AF: 0.00334

Gnomad NFE exome AF: 0.00261

Gnomad OTH exome AF: 0.00548

GnomAD4 exome AF: 0.00431 AC: 4906 AN: 1137730 Hom.: 0 Cov.: 22 AF XY: 0.00400 AC XY: 2266 AN XY: 567132

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

African (AFR) AF: 0.00501 AC: 128 AN: 25546

American (AMR) AF: 0.00358 AC: 121 AN: 33846

Ashkenazi Jewish (ASJ) AF: 0.00279 AC: 55 AN: 19708

East Asian (EAS) AF: 0.00912 AC: 284 AN: 31148

South Asian (SAS) AF: 0.00408 AC: 262 AN: 64256

European-Finnish (FIN) AF: 0.00192 AC: 82 AN: 42644

Middle Eastern (MID) AF: 0.00464 AC: 22 AN: 4744

European-Non Finnish (NFE) AF: 0.00435 AC: 3783 AN: 869038

Other (OTH) AF: 0.00361 AC: 169 AN: 46800

⚠️ 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: 0.000755 AC: 112 AN: 148266 Hom.: 0 Cov.: 33 AF XY: 0.000706 AC XY: 51 AN XY: 72268

African (AFR) AF: 0.00138 AC: 56 AN: 40620

American (AMR) AF: 0.00128 AC: 19 AN: 14858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.00335 AC: 17 AN: 5080

South Asian (SAS) AF: 0.000641 AC: 3 AN: 4680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9808

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

European-Non Finnish (NFE) AF: 0.000255 AC: 17 AN: 66588

Other (OTH) AF: 0.00 AC: 0 AN: 2040

Alfa AF: 0.00816 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SNX10-related disorder (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)		0.040		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;