chr6-87473325-G-C

Variant names:

• chr6-87473325-G-C
• rs58785365
• NM_006416.5:c.16+306G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006416.5(SLC35A1):​c.16+306G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,930 control chromosomes in the GnomAD database, including 10,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (10917 hom., cov: 32)
• Consequence: SLC35A1 NM_006416.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.594
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-87473325-G-C is Benign according to our data. Variant chr6-87473325-G-C is described in ClinVar as Benign. ClinVar VariationId is 1296401.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.451 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+306G>C		intron	N/A	NP_006407.1	P78382-1
	SLC35A1	NM_001168398.2		c.16+306G>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.16+306G>C		intron	N/A	ENSP00000358565.4	P78382-1
	SLC35A1	ENST00000369556.7	TSL:1	c.16+306G>C		intron	N/A	ENSP00000358569.3	P78382-2
	ENSG00000213204	ENST00000507897.5	TSL:2	n.*61-4037G>C		intron	N/A	ENSP00000426769.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57360 AN: 151810 Hom.: 10904 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.378 AC: 57391 AN: 151930 Hom.: 10917 Cov.: 32 AF XY: 0.377 AC XY: 27950 AN XY: 74232

African (AFR) AF: 0.403 AC: 16705 AN: 41438

American (AMR) AF: 0.460 AC: 7029 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3472

East Asian (EAS) AF: 0.309 AC: 1585 AN: 5126

South Asian (SAS) AF: 0.372 AC: 1785 AN: 4798

European-Finnish (FIN) AF: 0.324 AC: 3426 AN: 10576

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

European-Non Finnish (NFE) AF: 0.358 AC: 24340 AN: 67928

Other (OTH) AF: 0.372 AC: 785 AN: 2112

Alfa AF: 0.364 Hom.: 1187

Bravo AF: 0.390

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.47
PhyloP100		-0.59
PromoterAI		-0.051	Neutral
Mutation Taster		=21/79	disease causing

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: rs58785365; hg19: chr6-88183043;