rs2333223

Positions:

• chr3-125447191-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003794.4(SNX4):​c.*588C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,552 control chromosomes in the GnomAD database, including 2,250 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 0.17 (2245 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5 hom.)
• Consequence: SNX4 NM_003794.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

Genes affected

SNX4 (HGNC:11175): (sorting nexin 4) 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 associated with the long isoform of the leptin receptor and with receptor tyrosine kinases for platelet-derived growth factor, insulin, and epidermal growth factor in cell cultures, but its function is unknown. This protein may form oligomeric complexes with family members. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX4	NM_003794.4	c.*588C>G		3_prime_UTR_variant	14/14	ENST00000251775.9	NP_003785.1
SNX4	XM_017007414.3	c.*588C>G		3_prime_UTR_variant	15/15		XP_016862903.1
SNX4	NR_073435.2	n.1849C>G		non_coding_transcript_exon_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX4	ENST00000251775	c.*588C>G		3_prime_UTR_variant	14/14	1	NM_003794.4	ENSP00000251775.4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25085 AN: 151994 Hom.: 2244 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.114 AC: 50 AN: 440 Hom.: 5 Cov.: 0 AF XY: 0.108 AC XY: 29 AN XY: 268

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.165 AC: 25119 AN: 152112 Hom.: 2245 Cov.: 32 AF XY: 0.166 AC XY: 12342 AN XY: 74368

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.160

Alfa AF: 0.145 Hom.: 254

Bravo AF: 0.175

Asia WGS AF: 0.212 AC: 736 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.5
DANN	Benign	0.84

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: rs2333223; hg19: chr3-125166035;