NM_006416.5:c.17-149C>T

Variant names:

• chr6-87477213-C-T
• rs78238771
• NM_006416.5:c.17-149C>T

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.17-149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 647,730 control chromosomes in the GnomAD database, including 798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (263 hom., cov: 32)
  • Exomes 𝑓: 0.040 (535 hom.)
• Consequence: SLC35A1 NM_006416.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.576
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-87477213-C-T is Benign according to our data. Variant chr6-87477213-C-T is described in ClinVar as Benign. ClinVar VariationId is 1248926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.084 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.17-149C>T		intron	N/A	NP_006407.1	P78382-1
	SLC35A1	NM_001168398.2		c.17-149C>T		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.17-149C>T		intron	N/A	ENSP00000358565.4	P78382-1
	SLC35A1	ENST00000369556.7	TSL:1	c.17-149C>T		intron	N/A	ENSP00000358569.3	P78382-2
	ENSG00000213204	ENST00000507897.5	TSL:2	n.*61-149C>T		intron	N/A	ENSP00000426769.1

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8307 AN: 151200 Hom.: 262 Cov.: 32

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0488

Gnomad OTH AF: 0.0558

GnomAD4 exome AF: 0.0398 AC: 19769 AN: 496412 Hom.: 535 AF XY: 0.0394 AC XY: 10400 AN XY: 263874

African (AFR) AF: 0.0862 AC: 1156 AN: 13410

American (AMR) AF: 0.0240 AC: 613 AN: 25552

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 306 AN: 15144

East Asian (EAS) AF: 0.000170 AC: 5 AN: 29378

South Asian (SAS) AF: 0.0256 AC: 1281 AN: 50066

European-Finnish (FIN) AF: 0.0621 AC: 1680 AN: 27054

Middle Eastern (MID) AF: 0.0232 AC: 47 AN: 2024

European-Non Finnish (NFE) AF: 0.0442 AC: 13564 AN: 306656

Other (OTH) AF: 0.0412 AC: 1117 AN: 27128

GnomAD4 genome AF: 0.0549 AC: 8309 AN: 151318 Hom.: 263 Cov.: 32 AF XY: 0.0546 AC XY: 4034 AN XY: 73934

African (AFR) AF: 0.0864 AC: 3546 AN: 41040

American (AMR) AF: 0.0318 AC: 484 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 72 AN: 3468

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5166

South Asian (SAS) AF: 0.0202 AC: 97 AN: 4810

European-Finnish (FIN) AF: 0.0624 AC: 648 AN: 10384

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0488 AC: 3311 AN: 67910

Other (OTH) AF: 0.0548 AC: 115 AN: 2100

Alfa AF: 0.0610 Hom.: 34

Bravo AF: 0.0534

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	-0.89
CADD	Benign	0.25
DANN	Benign	0.41
PhyloP100		-0.58
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: rs78238771; hg19: chr6-88186931;