7-17814952-GAAAA-GAA

Variant names:

• chr7-17814952-GAA-G
• rs34649849
• NM_015132.5:c.1954-10_1954-9delTT

Variant summary

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

The NM_015132.5(SNX13):​c.1954-10_1954-9delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000965 in 1,214,988 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), 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 0.000038 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: SNX13 NM_015132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 2 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.1954-10_1954-9delTT		intron	N/A	NP_055947.1	Q9Y5W8-2
	SNX13	NM_001350862.2		c.1987-10_1987-9delTT		intron	N/A	NP_001337791.1	Q9Y5W8-1
	SNX13	NM_001350863.2		c.1714-10_1714-9delTT		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.1954-10_1954-9delTT		intron	N/A	ENSP00000398789.2	Q9Y5W8-2
	SNX13	ENST00000611725.4	TSL:1	c.1987-10_1987-9delTT		intron	N/A	ENSP00000479044.1	A0A087WUZ7
	SNX13	ENST00000496855.1	TSL:1	n.298-10_298-9delTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000384 AC: 5 AN: 130354 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: 0.000487

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000335

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00108 AC: 1168 AN: 1084620 Hom.: 0 AF XY: 0.00119 AC XY: 625 AN XY: 527244

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

African (AFR) AF: 0.000620 AC: 13 AN: 20956

American (AMR) AF: 0.00240 AC: 23 AN: 9572

Ashkenazi Jewish (ASJ) AF: 0.00219 AC: 37 AN: 16932

East Asian (EAS) AF: 0.000607 AC: 15 AN: 24712

South Asian (SAS) AF: 0.00281 AC: 113 AN: 40284

European-Finnish (FIN) AF: 0.00357 AC: 109 AN: 30546

Middle Eastern (MID) AF: 0.000712 AC: 3 AN: 4212

European-Non Finnish (NFE) AF: 0.000905 AC: 808 AN: 893074

Other (OTH) AF: 0.00106 AC: 47 AN: 44332

⚠️ 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: 0.0000384 AC: 5 AN: 130368 Hom.: 0 Cov.: 0 AF XY: 0.0000320 AC XY: 2 AN XY: 62488

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

African (AFR) AF: 0.00 AC: 0 AN: 36586

American (AMR) AF: 0.00 AC: 0 AN: 12918

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4674

South Asian (SAS) AF: 0.00 AC: 0 AN: 4300

European-Finnish (FIN) AF: 0.000487 AC: 3 AN: 6158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.0000335 AC: 2 AN: 59750

Other (OTH) AF: 0.00 AC: 0 AN: 1788

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000452083), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
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;