rs2548621

Positions:

• chr5-54606509-G-A
• chr5-54606509-G-C

Variant summary

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

The XM_017008997.2(SNX18):​c.*102G>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 0.896 in 152,120 control chromosomes in the GnomAD database, including 62,168 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 0.90 (62168 hom., cov: 31)
• Consequence: SNX18 XM_017008997.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853

Genes affected

SNX18 (HGNC:19245): (sorting nexin 18) 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 some family members, but contains a SH3 domain. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX18	XM_017008997.2	c.*102G>A		3_prime_UTR_variant	2/2		XP_016864486.1
SNX18	XR_001741987.2	n.1919+3G>A		splice_region_variant, intron_variant
SNX18	XR_007058577.1	n.1919+3G>A		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.896 AC: 136241 AN: 152002 Hom.: 62151 Cov.: 31

Gnomad AFR AF: 0.704

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.896 AC: 136305 AN: 152120 Hom.: 62168 Cov.: 31 AF XY: 0.899 AC XY: 66864 AN XY: 74374

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.967

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.980

Gnomad4 FIN AF: 0.976

Gnomad4 NFE AF: 0.976

Gnomad4 OTH AF: 0.918

Alfa AF: 0.967 Hom.: 139354

Bravo AF: 0.884

Asia WGS AF: 0.947 AC: 3296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2548621; hg19: chr5-53902339;