chr6-87493123-G-A

Variant names:

• chr6-87493123-G-A
• rs9450716
• NM_006416.5:c.195-7385G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006416.5(SLC35A1):​c.195-7385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,736 control chromosomes in the GnomAD database, including 12,208 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12208 hom., cov: 30)
• Consequence: SLC35A1 NM_006416.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A1	NM_006416.5	c.195-7385G>A		intron_variant	Intron 2 of 7	ENST00000369552.9	NP_006407.1
SLC35A1	NM_001168398.2	c.195-7385G>A		intron_variant	Intron 2 of 6		NP_001161870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A1	ENST00000369552.9	c.195-7385G>A		intron_variant	Intron 2 of 7	1	NM_006416.5	ENSP00000358565.4
ENSG00000213204	ENST00000507897.5	n.*284-2952G>A		intron_variant	Intron 15 of 15	2		ENSP00000426769.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60305 AN: 151618 Hom.: 12195 Cov.: 30

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.398 AC: 60344 AN: 151736 Hom.: 12208 Cov.: 30 AF XY: 0.396 AC XY: 29335 AN XY: 74146

African (AFR) AF: 0.472 AC: 19501 AN: 41314

American (AMR) AF: 0.471 AC: 7174 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3464

East Asian (EAS) AF: 0.313 AC: 1618 AN: 5164

South Asian (SAS) AF: 0.373 AC: 1794 AN: 4816

European-Finnish (FIN) AF: 0.325 AC: 3415 AN: 10494

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

European-Non Finnish (NFE) AF: 0.358 AC: 24286 AN: 67932

Other (OTH) AF: 0.388 AC: 820 AN: 2116

Alfa AF: 0.371 Hom.: 43513

Bravo AF: 0.412

Asia WGS AF: 0.347 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.34
DANN	Benign	0.51
PhyloP100		-1.6
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: rs9450716; hg19: chr6-88202841;