7-17814952-GAAAA-GA

Variant names:

• chr7-17814952-GAAA-G
• rs34649849
• NM_015132.5:c.1954-11_1954-9delTTT

Variant summary

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

The NM_015132.5(SNX13):​c.1954-11_1954-9delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,092,004 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNX13 NM_015132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

Genes affected

SNX13 (HGNC:21335): (sorting nexin 13) This gene encodes a PHOX domain- and RGS domain-containing protein that belongs to the sorting nexin (SNX) family and the regulator of G protein signaling (RGS) family. The PHOX domain is a phosphoinositide binding domain, and the SNX family members are involved in intracellular trafficking. The RGS family members are regulatory molecules that act as GTPase activating proteins for G alpha subunits of heterotrimeric G proteins. The RGS domain of this protein interacts with G alpha(s), accelerates its GTP hydrolysis, and attenuates G alpha(s)-mediated signaling. Overexpression of this protein delayes lysosomal degradation of the epidermal growth factor receptor. Because of its bifunctional role, this protein may link heterotrimeric G protein signaling and vesicular trafficking. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015132.5. 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
	SNX13	NM_015132.5	MANE Select	c.1954-11_1954-9delTTT		intron	N/A	NP_055947.1	Q9Y5W8-2
	SNX13	NM_001350862.2		c.1987-11_1987-9delTTT		intron	N/A	NP_001337791.1	Q9Y5W8-1
	SNX13	NM_001350863.2		c.1714-11_1714-9delTTT		intron	N/A	NP_001337792.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX13	ENST00000428135.7	TSL:1 MANE Select	c.1954-11_1954-9delTTT		intron	N/A	ENSP00000398789.2	Q9Y5W8-2
	SNX13	ENST00000611725.4	TSL:1	c.1987-11_1987-9delTTT		intron	N/A	ENSP00000479044.1	A0A087WUZ7
	SNX13	ENST00000496855.1	TSL:1	n.298-11_298-9delTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 130362 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000103 AC: 112 AN: 1092004 Hom.: 0 AF XY: 0.000124 AC XY: 66 AN XY: 530932

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

African (AFR) AF: 0.000143 AC: 3 AN: 21020

American (AMR) AF: 0.000207 AC: 2 AN: 9684

Ashkenazi Jewish (ASJ) AF: 0.000117 AC: 2 AN: 17102

East Asian (EAS) AF: 0.0000805 AC: 2 AN: 24858

South Asian (SAS) AF: 0.000197 AC: 8 AN: 40604

European-Finnish (FIN) AF: 0.000388 AC: 12 AN: 30966

Middle Eastern (MID) AF: 0.000236 AC: 1 AN: 4234

European-Non Finnish (NFE) AF: 0.0000868 AC: 78 AN: 898944

Other (OTH) AF: 0.0000897 AC: 4 AN: 44592

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 130362 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 62468

African (AFR) AF: 0.00 AC: 0 AN: 36528

American (AMR) AF: 0.00 AC: 0 AN: 12904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3160

East Asian (EAS) AF: 0.00 AC: 0 AN: 4686

South Asian (SAS) AF: 0.00 AC: 0 AN: 4330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 59764

Other (OTH) AF: 0.00 AC: 0 AN: 1776

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs34649849; hg19: chr7-17854575;