7-26371803-CTT-CTTTTTTTTT

Variant names:

• chr7-26371803-C-CTTTTTTT
• rs201825204
• NM_013322.3:c.312-14_312-8dupTTTTTTT

Variant summary

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

The NM_013322.3(SNX10):​c.312-14_312-8dupTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000857 in 1,166,280 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: SNX10 NM_013322.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 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.312-14_312-8dupTTTTTTT		splice_region intron	N/A	NP_037454.2
	SNX10	NM_001318198.1		c.390-14_390-8dupTTTTTTT		splice_region intron	N/A	NP_001305127.1	Q9Y5X0
	SNX10	NM_001362753.1		c.390-14_390-8dupTTTTTTT		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.312-14_312-8dupTTTTTTT		splice_region intron	N/A	ENSP00000343709.5	Q9Y5X0-1
	SNX10	ENST00000396376.5	TSL:1	c.312-14_312-8dupTTTTTTT		splice_region intron	N/A	ENSP00000379661.1	Q9Y5X0-1
	SNX10	ENST00000446848.6	TSL:1	c.312-14_312-8dupTTTTTTT		splice_region intron	N/A	ENSP00000395474.3	Q9Y5X0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.57e-7 AC: 1 AN: 1166280 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 581152

⚠️ 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: 26188

American (AMR) AF: 0.0000289 AC: 1 AN: 34578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20274

East Asian (EAS) AF: 0.00 AC: 0 AN: 31986

South Asian (SAS) AF: 0.00 AC: 0 AN: 66104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4830

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 890784

Other (OTH) AF: 0.00 AC: 0 AN: 47920

⚠️ 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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.49

Splicing

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

Other links and lift over

dbSNP: rs201825204; hg19: chr7-26411423;