1-67029600-A-G

Variant names:

• chr1-67029600-A-G
• rs2755250
• NM_015139.3:c.730-7998T>C

Variant summary

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

The NM_015139.3(SLC35D1):​c.730-7998T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,130 control chromosomes in the GnomAD database, including 46,445 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 0.78 (46445 hom., cov: 31)
• Consequence: SLC35D1 NM_015139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015139.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35D1	NM_015139.3	MANE Select	c.730-7998T>C		intron	N/A	NP_055954.1	Q9NTN3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35D1	ENST00000235345.6	TSL:1 MANE Select	c.730-7998T>C		intron	N/A	ENSP00000235345.5	Q9NTN3-1
	SLC35D1	ENST00000901512.1		c.810+2424T>C		intron	N/A	ENSP00000571571.1
	SLC35D1	ENST00000901514.1		c.727-7998T>C		intron	N/A	ENSP00000571573.1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118372 AN: 152012 Hom.: 46405 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.779 AC: 118468 AN: 152130 Hom.: 46445 Cov.: 31 AF XY: 0.779 AC XY: 57880 AN XY: 74318

African (AFR) AF: 0.823 AC: 34175 AN: 41520

American (AMR) AF: 0.830 AC: 12665 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2863 AN: 3472

East Asian (EAS) AF: 0.878 AC: 4537 AN: 5170

South Asian (SAS) AF: 0.882 AC: 4259 AN: 4830

European-Finnish (FIN) AF: 0.638 AC: 6730 AN: 10554

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50630 AN: 68004

Other (OTH) AF: 0.786 AC: 1659 AN: 2110

Alfa AF: 0.761 Hom.: 21429

Bravo AF: 0.792

Asia WGS AF: 0.873 AC: 3037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.75
PhyloP100		-0.52
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: rs2755250; hg19: chr1-67495283;