chr1-67047012-A-G

Variant names:

• chr1-67047012-A-G
• rs1024228
• NM_015139.3:c.636+253T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 VariationId 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.

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.636+253T>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.636+253T>C		intron	N/A	ENSP00000235345.5	Q9NTN3-1
	SLC35D1	ENST00000901512.1		c.636+253T>C		intron	N/A	ENSP00000571571.1
	SLC35D1	ENST00000901514.1		c.636+253T>C		intron	N/A	ENSP00000571573.1

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

African (AFR) AF: 0.830 AC: 34480 AN: 41522

American (AMR) AF: 0.719 AC: 10976 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2772 AN: 3468

East Asian (EAS) AF: 0.620 AC: 3208 AN: 5178

South Asian (SAS) AF: 0.764 AC: 3677 AN: 4810

European-Finnish (FIN) AF: 0.596 AC: 6301 AN: 10572

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48774 AN: 67972

Other (OTH) AF: 0.735 AC: 1553 AN: 2114

Alfa AF: 0.728 Hom.: 29442

Bravo AF: 0.752

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.94
DANN	Benign	0.22
PhyloP100		-0.22
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: rs1024228; hg19: chr1-67512695;