rs1051131

chr6-87511828-A-G

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.*302A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 381,954 control chromosomes in the GnomAD database, including 64,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (29023 hom., cov: 31)
  • Exomes 𝑓: 0.55 (35950 hom.)
• Consequence: SLC35A1 NM_006416.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.629

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=-0.49).
• BP6: Variant 6-87511828-A-G is Benign according to our data. Variant chr6-87511828-A-G is described in ClinVar as [Benign]. Clinvar id is 358221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A1	NM_006416.5	c.*302A>G		3_prime_UTR_variant	8/8	ENST00000369552.9
SLC35A1	NM_001168398.2	c.*302A>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A1	ENST00000369552.9	c.*302A>G		3_prime_UTR_variant	8/8	1	NM_006416.5	P1
SLC35A1	ENST00000369556.7	c.*302A>G		3_prime_UTR_variant	7/7	1
SLC35A1	ENST00000369557.9	c.*502A>G		3_prime_UTR_variant	6/6	2
SLC35A1	ENST00000464978.5			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92508 AN: 151868 Hom.: 28975 Cov.: 31

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.555 AC: 127542 AN: 229966 Hom.: 35950 Cov.: 2 AF XY: 0.553 AC XY: 69266 AN XY: 125240

Gnomad4 AFR exome AF: 0.754

Gnomad4 AMR exome AF: 0.683

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.568

Gnomad4 SAS exome AF: 0.560

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome AF: 0.609 AC: 92621 AN: 151988 Hom.: 29023 Cov.: 31 AF XY: 0.608 AC XY: 45158 AN XY: 74278

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.600

Alfa AF: 0.573 Hom.: 9753

Bravo AF: 0.629

Asia WGS AF: 0.635 AC: 2204 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Pontoneocerebellar hypoplasia Benign:1

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	-0.49
Cadd	Benign	14
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1051131; hg19: chr6-88221546; COSMIC: COSV65761432; COSMIC: COSV65761432;