XM_047415662.1:c.*24+9208A>G

Variant names:

• chr1-66995108-T-C
• rs4486425
• XM_047415662.1:c.*24+9208A>G

Variant summary

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

The XM_047415662.1(SLC35D1):​c.*24+9208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,854 control chromosomes in the GnomAD database, including 15,521 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 0.42 (15521 hom., cov: 29)
• Consequence: SLC35D1 XM_047415662.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 2 publications found

Genes affected

SLC35D1 (HGNC:20800): (solute carrier family 35 member D1) Glycosylation of cellular glycoconjugates occurs in the endoplasmic reticulum (ER) and Golgi compartment, and requires transport of nucleotide sugars from the cytosol into the lumen of the ER and Golgi by specific transporters. The protein encoded by this gene resides in the ER, and transports both UDP-glucuronic acid (UDP-GlcA) and UDP-N-acetylgalactosamine (UDP-GalNAc) from the cytoplasm to the ER lumen. It may participate in glucuronidation and/or chondroitin sulfate biosynthesis. Mutations in this gene are associated with Schneckenbecken dysplasia.[provided by RefSeq, Sep 2009]

SLC35D1 Gene-Disease associations (from GenCC):

• schneckenbecken dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35D1	XM_047415662.1	c.*24+9208A>G		intron_variant	Intron 12 of 12		XP_047271618.1
SLC35D1	XM_047415665.1	c.*24+9208A>G		intron_variant	Intron 12 of 12		XP_047271621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63620 AN: 151736 Hom.: 15488 Cov.: 29

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.419 AC: 63693 AN: 151854 Hom.: 15521 Cov.: 29 AF XY: 0.415 AC XY: 30789 AN XY: 74204

African (AFR) AF: 0.673 AC: 27854 AN: 41410

American (AMR) AF: 0.291 AC: 4439 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3466

East Asian (EAS) AF: 0.163 AC: 838 AN: 5156

South Asian (SAS) AF: 0.234 AC: 1128 AN: 4812

European-Finnish (FIN) AF: 0.418 AC: 4393 AN: 10514

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23055 AN: 67906

Other (OTH) AF: 0.391 AC: 826 AN: 2112

Alfa AF: 0.362 Hom.: 31745

Bravo AF: 0.422

Asia WGS AF: 0.241 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.66
DANN	Benign	0.58
PhyloP100		-0.59

Splicing

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

Other links and lift over

dbSNP: rs4486425; hg19: chr1-67460791; COSMIC: COSV52430350;