rs9264

Variant names:

• chr14-34562963-C-T
• rs9264
• NM_152233.4:c.*159G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152233.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX6	NM_152233.4	MANE Select	c.*159G>A		3_prime_UTR	Exon 14 of 14	NP_689419.3	Q9UNH7-1
	SNX6	NM_001366519.1		c.*159G>A		3_prime_UTR	Exon 13 of 13	NP_001353448.1
	SNX6	NM_021249.5		c.*159G>A		3_prime_UTR	Exon 13 of 13	NP_067072.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX6	ENST00000362031.10	TSL:1 MANE Select	c.*159G>A		3_prime_UTR	Exon 14 of 14	ENSP00000355217.5	Q9UNH7-1
	SNX6	ENST00000396526.7	TSL:1	c.*159G>A		3_prime_UTR	Exon 13 of 13	ENSP00000379779.3	Q9UNH7-2
	SNX6	ENST00000882741.1		c.*159G>A		3_prime_UTR	Exon 15 of 15	ENSP00000552800.1

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

African (AFR) AF: 0.0659 AC: 912 AN: 13842

American (AMR) AF: 0.189 AC: 4058 AN: 21432

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 4546 AN: 14918

East Asian (EAS) AF: 0.111 AC: 3512 AN: 31566

South Asian (SAS) AF: 0.273 AC: 13126 AN: 48142

European-Finnish (FIN) AF: 0.309 AC: 13837 AN: 44840

Middle Eastern (MID) AF: 0.304 AC: 686 AN: 2254

European-Non Finnish (NFE) AF: 0.372 AC: 121087 AN: 325826

Other (OTH) AF: 0.299 AC: 8512 AN: 28488

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

African (AFR) AF: 0.0690 AC: 2870 AN: 41566

American (AMR) AF: 0.217 AC: 3309 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3472

East Asian (EAS) AF: 0.0941 AC: 488 AN: 5184

South Asian (SAS) AF: 0.277 AC: 1335 AN: 4820

European-Finnish (FIN) AF: 0.301 AC: 3186 AN: 10572

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25407 AN: 68000

Other (OTH) AF: 0.265 AC: 560 AN: 2114

Alfa AF: 0.287 Hom.: 5305

Bravo AF: 0.236

Asia WGS AF: 0.195 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.71
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9264; hg19: chr14-35032169;