rs56136150

Positions:

• chr6-87511385-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006416.5(SLC35A1):​c.887-14T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 1,612,446 control chromosomes in the GnomAD database, including 8,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (924 hom., cov: 32)
  • Exomes 𝑓: 0.099 (7414 hom.)
• Consequence: SLC35A1 NM_006416.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.116

Genes affected

SLC35A1 (HGNC:11021): (solute carrier family 35 member A1) The protein encoded by this gene is found in the membrane of the Golgi apparatus, where it transports nucleotide sugars into the Golgi. One such nucleotide sugar is CMP-sialic acid, which is imported into the Golgi by the encoded protein and subsequently glycosylated. Defects in this gene are a cause of congenital disorder of glycosylation type 2F (CDG2F). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-87511385-T-C is Benign according to our data. Variant chr6-87511385-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 95394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35A1	NM_006416.5	c.887-14T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000369552.9	NP_006407.1
SLC35A1	NM_001168398.2	c.710-14T>C		splice_polypyrimidine_tract_variant, intron_variant			NP_001161870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35A1	ENST00000369552.9	c.887-14T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006416.5	ENSP00000358565	P1
SLC35A1	ENST00000369556.7	c.710-14T>C		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000358569
SLC35A1	ENST00000369557.9	c.*73-14T>C		splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000358570
SLC35A1	ENST00000464978.5	n.895-14T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16347 AN: 152030 Hom.: 923 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0968

Gnomad OTH AF: 0.106

GnomAD3 exomes AF: 0.106 AC: 26629 AN: 251038 Hom.: 1489 AF XY: 0.105 AC XY: 14225 AN XY: 135740

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.0869

Gnomad EAS exome AF: 0.168

Gnomad SAS exome AF: 0.0981

Gnomad FIN exome AF: 0.0980

Gnomad NFE exome AF: 0.0975

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0987 AC: 144101 AN: 1460298 Hom.: 7414 Cov.: 33 AF XY: 0.0984 AC XY: 71462 AN XY: 726540

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.0869

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0994

Gnomad4 NFE exome AF: 0.0952

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.108 AC: 16366 AN: 152148 Hom.: 924 Cov.: 32 AF XY: 0.107 AC XY: 7989 AN XY: 74388

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0969

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0966 Hom.: 189

Bravo AF: 0.113

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 09, 2012	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

SLC35A1-congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Pontoneocerebellar hypoplasia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.71

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: rs56136150; hg19: chr6-88221103; COSMIC: COSV65761289; COSMIC: COSV65761289;