rs56136150

Variant names:

• chr6-87511385-T-C
• rs56136150
• NM_006416.5:c.887-14T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006416.5(SLC35A1):​c.887-14T>C variant causes a 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 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.116
• Publications: 5 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ENSG00000213204 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

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.887-14T>C		intron	N/A	NP_006407.1	P78382-1
	SLC35A1	NM_001168398.2		c.710-14T>C		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.887-14T>C		intron	N/A	ENSP00000358565.4	P78382-1
	SLC35A1	ENST00000369556.7	TSL:1	c.710-14T>C		intron	N/A	ENSP00000358569.3	P78382-2
	SLC35A1	ENST00000894726.1		c.932-14T>C		intron	N/A	ENSP00000564785.1

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

GnomAD2 exomes AF: 0.106 AC: 26629 AN: 251038 AF XY: 0.105

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 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

African (AFR) AF: 0.119 AC: 3981 AN: 33452

American (AMR) AF: 0.117 AC: 5222 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 2269 AN: 26116

East Asian (EAS) AF: 0.154 AC: 6124 AN: 39646

South Asian (SAS) AF: 0.102 AC: 8755 AN: 86214

European-Finnish (FIN) AF: 0.0994 AC: 5279 AN: 53124

Middle Eastern (MID) AF: 0.114 AC: 658 AN: 5758

European-Non Finnish (NFE) AF: 0.0952 AC: 105706 AN: 1110914

Other (OTH) AF: 0.101 AC: 6107 AN: 60354

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

African (AFR) AF: 0.116 AC: 4804 AN: 41486

American (AMR) AF: 0.126 AC: 1921 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3472

East Asian (EAS) AF: 0.155 AC: 803 AN: 5188

South Asian (SAS) AF: 0.105 AC: 508 AN: 4822

European-Finnish (FIN) AF: 0.101 AC: 1069 AN: 10588

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0969 AC: 6588 AN: 67996

Other (OTH) AF: 0.108 AC: 228 AN: 2110

Alfa AF: 0.0990 Hom.: 298

Bravo AF: 0.113

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Congenital disorder of glycosylation (1)
-	-	1	not provided (1)
-	-	1	Pontoneocerebellar hypoplasia (1)
-	-	1	SLC35A1-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.71
PhyloP100		0.12
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

Other links and lift over

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