7-17814952-GAAAA-GAAAAAAAA

Variant names:

• chr7-17814952-G-GAAAA
• rs34649849
• NM_015132.5:c.1954-12_1954-9dupTTTT

Variant summary

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

The NM_015132.5(SNX13):​c.1954-12_1954-9dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), 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 0.000015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00092 (1 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX13	NM_015132.5	c.1954-12_1954-9dupTTTT		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_1954-8insTTTT		intron_variant	Intron 19 of 25	1	NM_015132.5	ENSP00000398789.2
SNX13	ENST00000611725.4	c.1987-9_1987-8insTTTT		intron_variant	Intron 19 of 24	1		ENSP00000479044.1
SNX13	ENST00000496855.1	n.298-9_298-8insTTTT		intron_variant	Intron 2 of 8	1
SNX13	ENST00000409076.6	n.*1652-9_*1652-8insTTTT		intron_variant	Intron 20 of 26	2		ENSP00000387053.2

Frequencies

GnomAD3 genomes AF: 0.0000153 AC: 2 AN: 130358 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000231

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00179 AC: 61 AN: 34130 AF XY: 0.00173

Gnomad AFR exome AF: 0.00306

Gnomad AMR exome AF: 0.000853

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00161

Gnomad OTH exome AF: 0.00287

GnomAD4 exome AF: 0.000918 AC: 1001 AN: 1089834 Hom.: 1 Cov.: 12 AF XY: 0.00100 AC XY: 532 AN XY: 529948

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

African (AFR) AF: 0.00162 AC: 34 AN: 20938

American (AMR) AF: 0.00165 AC: 16 AN: 9672

Ashkenazi Jewish (ASJ) AF: 0.00105 AC: 18 AN: 17072

East Asian (EAS) AF: 0.00125 AC: 31 AN: 24750

South Asian (SAS) AF: 0.00360 AC: 146 AN: 40526

European-Finnish (FIN) AF: 0.000807 AC: 25 AN: 30966

Middle Eastern (MID) AF: 0.000237 AC: 1 AN: 4228

European-Non Finnish (NFE) AF: 0.000755 AC: 677 AN: 897164

Other (OTH) AF: 0.00119 AC: 53 AN: 44518

⚠️ 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: 0.0000153 AC: 2 AN: 130358 Hom.: 0 Cov.: 0 AF XY: 0.0000160 AC XY: 1 AN XY: 62466

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

African (AFR) AF: 0.0000274 AC: 1 AN: 36528

American (AMR) AF: 0.00 AC: 0 AN: 12904

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4686

South Asian (SAS) AF: 0.000231 AC: 1 AN: 4330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 59760

Other (OTH) AF: 0.00 AC: 0 AN: 1776

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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;