5-122819664-G-C

Variant names:

• chr5-122819664-G-C
• rs7718104
• NM_003100.4:c.1212+641G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003100.4(SNX2):​c.1212+641G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,110 control chromosomes in the GnomAD database, including 3,599 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 0.20 (3599 hom., cov: 33)
• Consequence: SNX2 NM_003100.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 2 publications found

Genes affected

SNX2 (HGNC:11173): (sorting nexin 2) This gene belongs to the sorting nexin family whose members contain the phosphoinositide-binding phox (PX) domain. The encoded protein is a component of the retromer complex which plays a role in protein sorting in the endocytic pathway. This protein may form oligomeric complexes with other family members. Alternate splicing results in multiple transcript variants of this gene. Pseudogenes associated with this gene are located on chromosomes 1 and 7. [provided by RefSeq, May 2013]

LOC105379154 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX2	NM_003100.4	c.1212+641G>C		intron_variant	Intron 11 of 14	ENST00000379516.7	NP_003091.2
SNX2	NM_001278199.1	c.861+641G>C		intron_variant	Intron 11 of 14		NP_001265128.1
LOC105379154	XR_007058917.1	n.1176+24710C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX2	ENST00000379516.7	c.1212+641G>C		intron_variant	Intron 11 of 14	1	NM_003100.4	ENSP00000368831.2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30981 AN: 151992 Hom.: 3587 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.204 AC: 31013 AN: 152110 Hom.: 3599 Cov.: 33 AF XY: 0.211 AC XY: 15673 AN XY: 74334

African (AFR) AF: 0.198 AC: 8225 AN: 41506

American (AMR) AF: 0.251 AC: 3836 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3470

East Asian (EAS) AF: 0.468 AC: 2420 AN: 5174

South Asian (SAS) AF: 0.395 AC: 1902 AN: 4820

European-Finnish (FIN) AF: 0.177 AC: 1866 AN: 10560

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11209 AN: 67986

Other (OTH) AF: 0.213 AC: 450 AN: 2112

Alfa AF: 0.0647 Hom.: 85

Bravo AF: 0.209

Asia WGS AF: 0.380 AC: 1319 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0090
DANN	Benign	0.59
PhyloP100		-2.0
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: rs7718104; hg19: chr5-122155359;