rs1372861855

Variant names:

• chr6-87511391-C-T
• rs1372861855
• NM_006416.5:c.887-8C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-87511391-C-T
• chr6-87511391-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006416.5(SLC35A1):​c.887-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC35A1 NM_006416.5 splice_region, intron
• Scores: Splicing: ADA: 0.0003551
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.235
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-87511391-C-T is Benign according to our data. Variant chr6-87511391-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 468944.Status of the report is criteria_provided_single_submitter, 1 stars.

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.887-8C>T		splice_region intron	N/A	NP_006407.1	P78382-1
	SLC35A1	NM_001168398.2		c.710-8C>T		splice_region 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.887-8C>T		splice_region intron	N/A	ENSP00000358565.4	P78382-1
	SLC35A1	ENST00000369556.7	TSL:1	c.710-8C>T		splice_region intron	N/A	ENSP00000358569.3	P78382-2
	SLC35A1	ENST00000894726.1		c.932-8C>T		splice_region intron	N/A	ENSP00000564785.1

Frequencies

GnomAD3 genomes AF: 0.000168 AC: 25 AN: 148828 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000493

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000179

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000909 AC: 214 AN: 235304 AF XY: 0.000730

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.000768

Gnomad ASJ exome AF: 0.00148

Gnomad EAS exome AF: 0.000581

Gnomad FIN exome AF: 0.000779

Gnomad NFE exome AF: 0.00100

Gnomad OTH exome AF: 0.00144

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000327 AC: 472 AN: 1444596 Hom.: 0 Cov.: 32 AF XY: 0.000285 AC XY: 205 AN XY: 718592

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00208 AC: 67 AN: 32230

American (AMR) AF: 0.00305 AC: 125 AN: 40940

Ashkenazi Jewish (ASJ) AF: 0.00102 AC: 26 AN: 25582

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39562

South Asian (SAS) AF: 0.0000838 AC: 7 AN: 83574

European-Finnish (FIN) AF: 0.000524 AC: 27 AN: 51536

Middle Eastern (MID) AF: 0.00159 AC: 9 AN: 5658

European-Non Finnish (NFE) AF: 0.000163 AC: 180 AN: 1105918

Other (OTH) AF: 0.000503 AC: 30 AN: 59596

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000168 AC: 25 AN: 148828 Hom.: 0 Cov.: 32 AF XY: 0.000207 AC XY: 15 AN XY: 72452

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000493 AC: 2 AN: 40538

American (AMR) AF: 0.00 AC: 0 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.00115 AC: 11 AN: 9592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000179 AC: 12 AN: 67070

Other (OTH) AF: 0.00 AC: 0 AN: 2050

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00929 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	SLC35A1-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.7
DANN	Benign	0.57
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00036
dbscSNV1_RF	Benign	0.0040
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: rs1372861855; hg19: chr6-88221109; COSMIC: COSV65761567; COSMIC: COSV65761567;