1-67009073-ATTT-ATTTT

Variant names:

• chr1-67009073-A-AT
• rs1433268625
• NM_015139.3:c.959+11dupA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015139.3(SLC35D1):​c.959+11dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000085 in 1,175,842 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: SLC35D1 NM_015139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.959+11dupA		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.959+11_959+12insA		intron	N/A	ENSP00000235345.5	Q9NTN3-1
	SLC35D1	ENST00000901512.1		c.1040+11_1040+12insA		intron	N/A	ENSP00000571571.1
	SLC35D1	ENST00000901514.1		c.956+11_956+12insA		intron	N/A	ENSP00000571573.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.50e-7 AC: 1 AN: 1175842 Hom.: 0 Cov.: 17 AF XY: 0.00000167 AC XY: 1 AN XY: 597900

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27798

American (AMR) AF: 0.00 AC: 0 AN: 43692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23864

East Asian (EAS) AF: 0.00 AC: 0 AN: 37742

South Asian (SAS) AF: 0.00 AC: 0 AN: 78950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5198

European-Non Finnish (NFE) AF: 0.00000117 AC: 1 AN: 856522

Other (OTH) AF: 0.00 AC: 0 AN: 50176

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.28

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: rs1433268625; hg19: chr1-67474756;