rs1024228

Positions:

• chr1-67047012-A-G
• chr1-67047012-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015139.3(SLC35D1):​c.636+253T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,106 control chromosomes in the GnomAD database, including 42,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (42061 hom., cov: 32)
• Consequence: SLC35D1 NM_015139.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.217

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-67047012-A-G is Benign according to our data. Variant chr1-67047012-A-G is described in ClinVar as [Benign]. Clinvar id is 1249477.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35D1	NM_015139.3	c.636+253T>C		intron_variant		ENST00000235345.6	NP_055954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35D1	ENST00000235345.6	c.636+253T>C		intron_variant		1	NM_015139.3	ENSP00000235345	P1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112487 AN: 151986 Hom.: 42031 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.740 AC: 112572 AN: 152106 Hom.: 42061 Cov.: 32 AF XY: 0.735 AC XY: 54678 AN XY: 74360

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.735

Alfa AF: 0.727 Hom.: 24030

Bravo AF: 0.752

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.94
DANN	Benign	0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs1024228; hg19: chr1-67512695;