rs9264

Positions:

• chr14-34562963-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152233.4(SNX6):​c.*159G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 683,520 control chromosomes in the GnomAD database, including 35,600 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (6242 hom., cov: 33)
  • Exomes 𝑓: 0.32 (29358 hom.)
• Consequence: SNX6 NM_152233.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

Genes affected

SNX6 (HGNC:14970): (sorting nexin 6) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein associates with the long isoform of the leptin receptor, the transforming growth factor-beta family of receptor serine-threonine kinases, and with receptor tyrosine kinases for platelet-derived growth factor, insulin, and epidermal growth factor. This protein may form oligomeric complexes with family member proteins through interactions of both the PX domain and the coiled coil regions of the molecules. Translocation of this protein from the cytoplasm to the nucleus occurs after binding to proviral integration site 1 protein. This gene results in two transcripts encoding two distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX6	NM_152233.4	c.*159G>A		3_prime_UTR_variant	14/14	ENST00000362031.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX6	ENST00000362031.10	c.*159G>A		3_prime_UTR_variant	14/14	1	NM_152233.4	P1
SNX6	ENST00000396526.7	c.*159G>A		3_prime_UTR_variant	13/13	1
SNX6	ENST00000652385.1	c.*159G>A		3_prime_UTR_variant	14/14
SNX6	ENST00000556162.6	c.*1447G>A		3_prime_UTR_variant, NMD_transcript_variant	15/15	2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38658 AN: 152094 Hom.: 6241 Cov.: 33

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.320 AC: 170276 AN: 531308 Hom.: 29358 Cov.: 7 AF XY: 0.322 AC XY: 90142 AN XY: 280210

Gnomad4 AFR exome AF: 0.0659

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.254 AC: 38659 AN: 152212 Hom.: 6242 Cov.: 33 AF XY: 0.249 AC XY: 18536 AN XY: 74408

Gnomad4 AFR AF: 0.0690

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.0941

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.265

Alfa AF: 0.326 Hom.: 3469

Bravo AF: 0.236

Asia WGS AF: 0.195 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9264; hg19: chr14-35032169;