7-17814952-GAAA-GAAAAAAA

Position:

• chr7-17814952-GAAA-GAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015132.5(SNX13):​c.1954-9_1954-8insTTTT variant causes a splice polypyrimidine tract, 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 0.000015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00092 (1 hom.)
• Consequence: SNX13 NM_015132.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 1001 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX13	NM_015132.5	c.1954-9_1954-8insTTTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000428135.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX13	ENST00000428135.7	c.1954-9_1954-8insTTTT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015132.5	P1
SNX13	ENST00000611725.4	c.1987-9_1987-8insTTTT		splice_polypyrimidine_tract_variant, intron_variant		1
SNX13	ENST00000496855.1	n.298-9_298-8insTTTT		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
SNX13	ENST00000409076.6	c.*1652-9_*1652-8insTTTT		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		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

GnomAD3 exomes AF: 0.00179 AC: 61 AN: 34130 Hom.: 0 AF XY: 0.00173 AC XY: 33 AN XY: 19058

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 SAS exome AF: 0.00276

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

Gnomad4 AFR exome AF: 0.00162

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00105

Gnomad4 EAS exome AF: 0.00125

Gnomad4 SAS exome AF: 0.00360

Gnomad4 FIN exome AF: 0.000807

Gnomad4 NFE exome AF: 0.000755

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.0000153 AC: 2 AN: 130358 Hom.: 0 Cov.: 0 AF XY: 0.0000160 AC XY: 1 AN XY: 62466

Gnomad4 AFR AF: 0.0000274

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000231

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34649849; hg19: chr7-17854575;