7-17814952-GAAAA-GAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015132.5(SNX13):​c.1954-10_1954-9dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (23898 hom., cov: 0)
  • Exomes 𝑓: 0.34 (7097 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNX13 NM_015132.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 7-17814952-G-GAA is Benign according to our data. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-17814952-G-GAA is described in CliVar as Benign. Clinvar id is 403464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX13	NM_015132.5	c.1954-10_1954-9dupTT		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_1954-8insTT		intron_variant	Intron 19 of 25	1	NM_015132.5	ENSP00000398789.2
SNX13	ENST00000611725.4	c.1987-9_1987-8insTT		intron_variant	Intron 19 of 24	1		ENSP00000479044.1
SNX13	ENST00000496855.1	n.298-9_298-8insTT		intron_variant	Intron 2 of 8	1
SNX13	ENST00000409076.6	n.*1652-9_*1652-8insTT		intron_variant	Intron 20 of 26	2		ENSP00000387053.2

Frequencies

GnomAD3 genomes AF: 0.620 AC: 80554 AN: 129904 Hom.: 23900 Cov.: 0

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.651

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.579

GnomAD2 exomes AF: 0.302 AC: 10292 AN: 34130 AF XY: 0.296

Gnomad AFR exome AF: 0.467

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.283

Gnomad EAS exome AF: 0.340

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.306

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.339 AC: 350628 AN: 1034566 Hom.: 7097 Cov.: 12 AF XY: 0.338 AC XY: 170246 AN XY: 503400

African (AFR) AF: 0.446 AC: 9070 AN: 20320

American (AMR) AF: 0.334 AC: 3100 AN: 9294

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 5508 AN: 16342

East Asian (EAS) AF: 0.410 AC: 9754 AN: 23780

South Asian (SAS) AF: 0.355 AC: 14049 AN: 39544

European-Finnish (FIN) AF: 0.250 AC: 7462 AN: 29864

Middle Eastern (MID) AF: 0.411 AC: 1658 AN: 4038

European-Non Finnish (NFE) AF: 0.336 AC: 285149 AN: 848926

Other (OTH) AF: 0.350 AC: 14878 AN: 42458

GnomAD4 genome AF: 0.620 AC: 80554 AN: 129918 Hom.: 23898 Cov.: 0 AF XY: 0.620 AC XY: 38578 AN XY: 62226

African (AFR) AF: 0.739 AC: 26944 AN: 36464

American (AMR) AF: 0.597 AC: 7675 AN: 12852

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 1978 AN: 3152

East Asian (EAS) AF: 0.731 AC: 3410 AN: 4666

South Asian (SAS) AF: 0.707 AC: 3036 AN: 4292

European-Finnish (FIN) AF: 0.450 AC: 2737 AN: 6088

Middle Eastern (MID) AF: 0.659 AC: 166 AN: 252

European-Non Finnish (NFE) AF: 0.557 AC: 33217 AN: 59590

Other (OTH) AF: 0.581 AC: 1036 AN: 1784

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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

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;