rs10638303

Variant names:

• chr6-87508882-C-CCACT
• rs10638303
• NM_006416.5:c.752-157_752-156insCTCA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006416.5(SLC35A1):​c.752-157_752-156insCTCA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (11337 hom., cov: 0)
• Consequence: SLC35A1 NM_006416.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -1.51
• Publications: 2 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: G2P, Labcorp Genetics (formerly Invitae)

ENSG00000213204 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-87508882-C-CCACT is Benign according to our data. Variant chr6-87508882-C-CCACT is described in ClinVar as Benign. ClinVar VariationId is 4843.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A1	NM_006416.5	MANE Select	c.752-157_752-156insCTCA		intron	N/A	NP_006407.1
	SLC35A1	NM_001168398.2		c.575-157_575-156insCTCA		intron	N/A	NP_001161870.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A1	ENST00000369552.9	TSL:1 MANE Select	c.752-159_752-158insCACT		intron	N/A	ENSP00000358565.4
	SLC35A1	ENST00000369556.7	TSL:1	c.575-159_575-158insCACT		intron	N/A	ENSP00000358569.3
	SLC35A1	ENST00000369557.9	TSL:2	c.508-159_508-158insCACT		intron	N/A	ENSP00000358570.5

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58500 AN: 151578 Hom.: 11323 Cov.: 0

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.386 AC: 58534 AN: 151696 Hom.: 11337 Cov.: 0 AF XY: 0.384 AC XY: 28448 AN XY: 74120

African (AFR) AF: 0.434 AC: 17920 AN: 41316

American (AMR) AF: 0.463 AC: 7045 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3466

East Asian (EAS) AF: 0.312 AC: 1610 AN: 5168

South Asian (SAS) AF: 0.373 AC: 1797 AN: 4824

European-Finnish (FIN) AF: 0.324 AC: 3411 AN: 10542

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24221 AN: 67860

Other (OTH) AF: 0.380 AC: 802 AN: 2110

Alfa AF: 0.378 Hom.: 1266

Bravo AF: 0.400

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	-	CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIf, MODIFIER OF (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10638303; hg19: chr6-88218600;