rs2268993

Variant names:

• chr6-87474393-G-A
• rs2268993
• NM_006416.5:c.16+1374G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

SLC35A1 Gene-Disease associations (from GenCC):

• SLC35A1-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000213204 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006416.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A1	NM_006416.5	MANE Select	c.16+1374G>A		intron	N/A	NP_006407.1	P78382-1
	SLC35A1	NM_001168398.2		c.16+1374G>A		intron	N/A	NP_001161870.1	P78382-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A1	ENST00000369552.9	TSL:1 MANE Select	c.16+1374G>A		intron	N/A	ENSP00000358565.4	P78382-1
	SLC35A1	ENST00000369556.7	TSL:1	c.16+1374G>A		intron	N/A	ENSP00000358569.3	P78382-2
	ENSG00000213204	ENST00000507897.5	TSL:2	n.*61-2969G>A		intron	N/A	ENSP00000426769.1

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

African (AFR) AF: 0.730 AC: 30316 AN: 41508

American (AMR) AF: 0.675 AC: 10309 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1704 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2645 AN: 5178

South Asian (SAS) AF: 0.561 AC: 2708 AN: 4826

European-Finnish (FIN) AF: 0.481 AC: 5064 AN: 10536

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36159 AN: 67976

Other (OTH) AF: 0.588 AC: 1243 AN: 2114

Alfa AF: 0.551 Hom.: 11855

Bravo AF: 0.620

Asia WGS AF: 0.612 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.0
DANN	Benign	0.80
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2268993;

hg19: chr6-88184111;