rs3800223

Positions:

• chr6-108251291-T-A
• chr6-108251291-T-C

Variant summary

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

The NM_003795.6(SNX3):​c.162+9469A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,040 control chromosomes in the GnomAD database, including 10,614 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 0.34 (10614 hom., cov: 32)
• Consequence: SNX3 NM_003795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

Genes affected

SNX3 (HGNC:11174): (sorting nexin 3) 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 does not contain a coiled coil region, like most family members. This protein interacts with phosphatidylinositol-3-phosphate, and is involved in protein trafficking. A pseudogene of this gene is present on the sex chromosomes. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX3	NM_003795.6	c.162+9469A>T		intron_variant		ENST00000230085.13	NP_003786.1
SNX3	NM_001300928.2	c.162+9469A>T		intron_variant			NP_001287857.1
SNX3	NM_001300929.2	c.96+9535A>T		intron_variant			NP_001287858.1
SNX3	NM_152827.4	c.162+9469A>T		intron_variant			NP_690040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX3	ENST00000230085.13	c.162+9469A>T		intron_variant		1	NM_003795.6	ENSP00000230085	P1
SNX3	ENST00000426155.6	c.162+9469A>T		intron_variant		1		ENSP00000401779
SNX3	ENST00000349379.5	c.96+9535A>T		intron_variant		2		ENSP00000296991
SNX3	ENST00000368979.6	c.162+9469A>T		intron_variant, NMD_transcript_variant		2		ENSP00000357975

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50946 AN: 151922 Hom.: 10614 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.336

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.335 AC: 50951 AN: 152040 Hom.: 10614 Cov.: 32 AF XY: 0.335 AC XY: 24871 AN XY: 74296

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.340

Alfa AF: 0.384 Hom.: 1586

Bravo AF: 0.324

Asia WGS AF: 0.417 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.61

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: rs3800223; hg19: chr6-108572495;