Genetic Variant SLC35D1:c.959+241_959+244delCTTG (chr1-67008840-TCAAG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_015139.3(SLC35D1):c.959+241_959+244delCTTG 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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.488

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35D1	NM_015139.3 link	c.959+241_959+244delCTTG		intron_variant	Intron 11 of 11	ENST00000235345.6	NP_055954.1	Q9NTN3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35D1	ENST00000235345.6 link	c.959+241_959+244delCTTG		intron_variant	Intron 11 of 11	1	NM_015139.3	ENSP00000235345.5		Q9NTN3-1

Frequencies

GnomAD3 genomes

AF:

0.00949

AC:

1442

AN:

152006

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00842

AC XY:

626

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00308

AC:

128

AN:

41494

American (AMR)

AF:

0.00975

AC:

149

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5142

South Asian (SAS)

AF:

0.00996

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0155

AC:

1053

AN:

67998

Other (OTH)

AF:

0.00854

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

143

215

286

358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00921

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 10, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.49

Mutation Taster

=100/0

polymorphism

(source)

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

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chr1-67008840-TCAAG-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

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