7-17814952-GAAAA-GAAAAA

Variant names:

• chr7-17814952-G-GA
• rs34649849
• NM_015132.5:c.1954-9dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_015132.5(SNX13):​c.1954-9dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (61 hom., cov: 0)
  • Exomes 𝑓: 0.11 (90 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0162 (2108/130330) while in subpopulation AFR AF = 0.0494 (1806/36582). AF 95% confidence interval is 0.0475. There are 61 homozygotes in GnomAd4. There are 1020 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2108 AD gene.

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.1954-9dupT		intron	N/A	NP_055947.1	Q9Y5W8-2
	SNX13	NM_001350862.2		c.1987-9dupT		intron	N/A	NP_001337791.1	Q9Y5W8-1
	SNX13	NM_001350863.2		c.1714-9dupT		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.1954-9_1954-8insT		intron	N/A	ENSP00000398789.2	Q9Y5W8-2
	SNX13	ENST00000611725.4	TSL:1	c.1987-9_1987-8insT		intron	N/A	ENSP00000479044.1	A0A087WUZ7
	SNX13	ENST00000496855.1	TSL:1	n.298-9_298-8insT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2104 AN: 130318 Hom.: 61 Cov.: 0

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.00513

Gnomad AMR AF: 0.00558

Gnomad ASJ AF: 0.000949

Gnomad EAS AF: 0.00470

Gnomad SAS AF: 0.000924

Gnomad FIN AF: 0.00309

Gnomad MID AF: 0.00735

Gnomad NFE AF: 0.00248

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.145 AC: 4933 AN: 34130 AF XY: 0.149

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.185

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.111 AC: 111562 AN: 1003078 Hom.: 90 Cov.: 12 AF XY: 0.112 AC XY: 54448 AN XY: 488090

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

African (AFR) AF: 0.179 AC: 3427 AN: 19148

American (AMR) AF: 0.132 AC: 1205 AN: 9112

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 1987 AN: 16084

East Asian (EAS) AF: 0.149 AC: 3406 AN: 22922

South Asian (SAS) AF: 0.128 AC: 4954 AN: 38568

European-Finnish (FIN) AF: 0.110 AC: 3254 AN: 29512

Middle Eastern (MID) AF: 0.108 AC: 426 AN: 3948

European-Non Finnish (NFE) AF: 0.107 AC: 88029 AN: 822496

Other (OTH) AF: 0.118 AC: 4874 AN: 41288

⚠️ 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: 0.0162 AC: 2108 AN: 130330 Hom.: 61 Cov.: 0 AF XY: 0.0163 AC XY: 1020 AN XY: 62460

African (AFR) AF: 0.0494 AC: 1806 AN: 36582

American (AMR) AF: 0.00558 AC: 72 AN: 12908

Ashkenazi Jewish (ASJ) AF: 0.000949 AC: 3 AN: 3160

East Asian (EAS) AF: 0.00471 AC: 22 AN: 4672

South Asian (SAS) AF: 0.000930 AC: 4 AN: 4300

European-Finnish (FIN) AF: 0.00309 AC: 19 AN: 6158

Middle Eastern (MID) AF: 0.00397 AC: 1 AN: 252

European-Non Finnish (NFE) AF: 0.00248 AC: 148 AN: 59728

Other (OTH) AF: 0.0162 AC: 29 AN: 1790

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34649849; hg19: chr7-17854575; COSMIC: COSV68069049; COSMIC: COSV68069049;