rs2268993

chr6-87474393-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006416.5(SLC35A1):c.16+1374G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,088 control chromosomes in the GnomAD database, including 27,901 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (27901 hom., cov: 33)
• Consequence: SLC35A1 NM_006416.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A1	NM_006416.5	c.16+1374G>A		intron_variant		ENST00000369552.9
SLC35A1	NM_001168398.2	c.16+1374G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A1	ENST00000369552.9	c.16+1374G>A		intron_variant		1	NM_006416.5	P1
SLC35A1	ENST00000369556.7	c.16+1374G>A		intron_variant		1
SLC35A1	ENST00000369557.9	c.16+1374G>A		intron_variant		2
SLC35A1	ENST00000464978.5	n.92-2969G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90743 AN: 151970 Hom.: 27854 Cov.: 33

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.597 AC: 90851 AN: 152088 Hom.: 27901 Cov.: 33 AF XY: 0.594 AC XY: 44174 AN XY: 74332

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.588

Alfa AF: 0.549 Hom.: 10507

Bravo AF: 0.620

Asia WGS AF: 0.612 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	8.0
Dann	Benign	0.80

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: rs2268993; hg19: chr6-88184111;