1-67008840-TCAAG-T

Position:

• chr1-67008840-TCAAG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_015139.3(SLC35D1):​c.959+241_959+244del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00947 in 152,124 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0095 (14 hom., cov: 32)
• Consequence: SLC35D1 NM_015139.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.488

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 -10 ACMG points.

• BP6: Variant 1-67008840-TCAAG-T is Benign according to our data. Variant chr1-67008840-TCAAG-T is described in ClinVar as [Likely_benign]. Clinvar id is 1179562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00947 (1440/152124) while in subpopulation NFE AF= 0.0155 (1053/67998). AF 95% confidence interval is 0.0147. There are 14 homozygotes in gnomad4. There are 626 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35D1	NM_015139.3	c.959+241_959+244del		intron_variant		ENST00000235345.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35D1	ENST00000235345.6	c.959+241_959+244del		intron_variant		1	NM_015139.3	P1

Frequencies

GnomAD3 genomes AF: 0.00949 AC: 1442 AN: 152006 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00309

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00976

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00995

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.00863

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

GnomAD4 genome AF: 0.00947 AC: 1440 AN: 152124 Hom.: 14 Cov.: 32 AF XY: 0.00842 AC XY: 626 AN XY: 74360

Gnomad4 AFR AF: 0.00308

Gnomad4 AMR AF: 0.00975

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00996

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.0155

Gnomad4 OTH AF: 0.00854

Alfa AF: 0.0109 Hom.: 1

Bravo AF: 0.00921

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs546709407; hg19: chr1-67474523;