chr6-108251291-T-A

Variant names:

• chr6-108251291-T-A
• rs3800223
• NM_003795.6:c.162+9469A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

SNX3 Gene-Disease associations (from GenCC):

• MMEP syndrome

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003795.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX3	NM_003795.6	MANE Select	c.162+9469A>T		intron	N/A	NP_003786.1
	SNX3	NM_001300929.2		c.96+9535A>T		intron	N/A	NP_001287858.1
	SNX3	NM_152827.4		c.162+9469A>T		intron	N/A	NP_690040.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX3	ENST00000230085.13	TSL:1 MANE Select	c.162+9469A>T		intron	N/A	ENSP00000230085.8
	SNX3	ENST00000426155.6	TSL:1	c.162+9469A>T		intron	N/A	ENSP00000401779.2
	SNX3	ENST00000349379.5	TSL:2	c.96+9535A>T		intron	N/A	ENSP00000296991.7

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

African (AFR) AF: 0.0849 AC: 3527 AN: 41532

American (AMR) AF: 0.350 AC: 5340 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1324 AN: 3470

East Asian (EAS) AF: 0.619 AC: 3187 AN: 5146

South Asian (SAS) AF: 0.275 AC: 1327 AN: 4818

European-Finnish (FIN) AF: 0.450 AC: 4742 AN: 10544

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30343 AN: 67952

Other (OTH) AF: 0.340 AC: 719 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.61
PhyloP100		0.35
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: rs3800223; hg19: chr6-108572495;