chr7-17814952-GA-G

Variant names:

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

Variant summary

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

The NM_015132.5(SNX13):​c.1954-9delT 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 0.0022 (0 hom., cov: 0)
  • Exomes 𝑓: 0.034 (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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 290 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 283 AN: 130306 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00561

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00186

Gnomad ASJ AF: 0.000317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000231

Gnomad FIN AF: 0.00325

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000502

Gnomad OTH AF: 0.00113

GnomAD2 exomes AF: 0.0894 AC: 3050 AN: 34130 AF XY: 0.0886

Gnomad AFR exome AF: 0.0306

Gnomad AMR exome AF: 0.0990

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.0643

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.0911

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0337 AC: 35034 AN: 1040898 Hom.: 0 Cov.: 12 AF XY: 0.0341 AC XY: 17281 AN XY: 506294

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

African (AFR) AF: 0.0120 AC: 250 AN: 20752

American (AMR) AF: 0.0462 AC: 433 AN: 9380

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 759 AN: 16464

East Asian (EAS) AF: 0.0202 AC: 492 AN: 24320

South Asian (SAS) AF: 0.0360 AC: 1428 AN: 39662

European-Finnish (FIN) AF: 0.0720 AC: 2120 AN: 29458

Middle Eastern (MID) AF: 0.0230 AC: 94 AN: 4090

European-Non Finnish (NFE) AF: 0.0328 AC: 28012 AN: 853976

Other (OTH) AF: 0.0338 AC: 1446 AN: 42796

⚠️ 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: 0.00223 AC: 290 AN: 130320 Hom.: 0 Cov.: 0 AF XY: 0.00234 AC XY: 146 AN XY: 62462

African (AFR) AF: 0.00579 AC: 212 AN: 36586

American (AMR) AF: 0.00186 AC: 24 AN: 12914

Ashkenazi Jewish (ASJ) AF: 0.000317 AC: 1 AN: 3158

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

South Asian (SAS) AF: 0.000233 AC: 1 AN: 4300

European-Finnish (FIN) AF: 0.00325 AC: 20 AN: 6158

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

European-Non Finnish (NFE) AF: 0.000502 AC: 30 AN: 59708

Other (OTH) AF: 0.00112 AC: 2 AN: 1788

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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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; COSMIC: COSV105339167; COSMIC: COSV105339167;