7-17814952-GAAAA-GAAAAAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_015132.5(SNX13):​c.1954-11_1954-9dupTTT 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 0.0020 (3 hom., cov: 0)
  • Exomes 𝑓: 0.043 (52 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 267 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX13	NM_015132.5	c.1954-11_1954-9dupTTT		intron_variant	Intron 19 of 25	ENST00000428135.7	NP_055947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX13	ENST00000428135.7	c.1954-9_1954-8insTTT		intron_variant	Intron 19 of 25	1	NM_015132.5	ENSP00000398789.2
SNX13	ENST00000611725.4	c.1987-9_1987-8insTTT		intron_variant	Intron 19 of 24	1		ENSP00000479044.1
SNX13	ENST00000496855.1	n.298-9_298-8insTTT		intron_variant	Intron 2 of 8	1
SNX13	ENST00000409076.6	n.*1652-9_*1652-8insTTT		intron_variant	Intron 20 of 26	2		ENSP00000387053.2

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 267 AN: 130340 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00101

Gnomad ASJ AF: 0.000949

Gnomad EAS AF: 0.00107

Gnomad SAS AF: 0.00300

Gnomad FIN AF: 0.000487

Gnomad MID AF: 0.00365

Gnomad NFE AF: 0.000854

Gnomad OTH AF: 0.000563

GnomAD2 exomes AF: 0.0360 AC: 1227 AN: 34130 AF XY: 0.0381

Gnomad AFR exome AF: 0.0544

Gnomad AMR exome AF: 0.0290

Gnomad ASJ exome AF: 0.0322

Gnomad EAS exome AF: 0.0498

Gnomad FIN exome AF: 0.0233

Gnomad NFE exome AF: 0.0360

Gnomad OTH exome AF: 0.0359

GnomAD4 exome AF: 0.0429 AC: 46037 AN: 1072292 Hom.: 52 Cov.: 12 AF XY: 0.0435 AC XY: 22656 AN XY: 521270

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

African (AFR) AF: 0.0847 AC: 1722 AN: 20328

American (AMR) AF: 0.0426 AC: 407 AN: 9546

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 784 AN: 16880

East Asian (EAS) AF: 0.0670 AC: 1629 AN: 24308

South Asian (SAS) AF: 0.0694 AC: 2773 AN: 39958

European-Finnish (FIN) AF: 0.0282 AC: 865 AN: 30670

Middle Eastern (MID) AF: 0.0427 AC: 177 AN: 4150

European-Non Finnish (NFE) AF: 0.0403 AC: 35561 AN: 882636

Other (OTH) AF: 0.0484 AC: 2119 AN: 43816

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00205 AC: 267 AN: 130354 Hom.: 3 Cov.: 0 AF XY: 0.00222 AC XY: 139 AN XY: 62478

African (AFR) AF: 0.00484 AC: 177 AN: 36582

American (AMR) AF: 0.00101 AC: 13 AN: 12916

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

East Asian (EAS) AF: 0.00107 AC: 5 AN: 4674

South Asian (SAS) AF: 0.00302 AC: 13 AN: 4300

European-Finnish (FIN) AF: 0.000487 AC: 3 AN: 6160

Middle Eastern (MID) AF: 0.00394 AC: 1 AN: 254

European-Non Finnish (NFE) AF: 0.000854 AC: 51 AN: 59738

Other (OTH) AF: 0.000559 AC: 1 AN: 1790

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Other links and lift over

dbSNP: rs34649849; hg19: chr7-17854575;