NM_006416.5:c.*302A>G

Variant names:

• chr6-87511828-A-G
• rs1051131
• NM_006416.5:c.*302A>G

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.*302A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 381,954 control chromosomes in the GnomAD database, including 64,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (29023 hom., cov: 31)
  • Exomes 𝑓: 0.55 (35950 hom.)
• Consequence: SLC35A1 NM_006416.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.629
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 6-87511828-A-G is Benign according to our data. Variant chr6-87511828-A-G is described in ClinVar as Benign. ClinVar VariationId is 358221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A1	NM_006416.5	c.*302A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000369552.9	NP_006407.1
SLC35A1	NM_001168398.2	c.*302A>G		3_prime_UTR_variant	Exon 7 of 7		NP_001161870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A1	ENST00000369552.9	c.*302A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_006416.5	ENSP00000358565.4

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92508 AN: 151868 Hom.: 28975 Cov.: 31

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.555 AC: 127542 AN: 229966 Hom.: 35950 Cov.: 2 AF XY: 0.553 AC XY: 69266 AN XY: 125240

African (AFR) AF: 0.754 AC: 5083 AN: 6740

American (AMR) AF: 0.683 AC: 7899 AN: 11568

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 2985 AN: 6028

East Asian (EAS) AF: 0.568 AC: 6282 AN: 11052

South Asian (SAS) AF: 0.560 AC: 21744 AN: 38846

European-Finnish (FIN) AF: 0.535 AC: 5428 AN: 10150

Middle Eastern (MID) AF: 0.520 AC: 461 AN: 886

European-Non Finnish (NFE) AF: 0.534 AC: 70994 AN: 132900

Other (OTH) AF: 0.565 AC: 6666 AN: 11796

GnomAD4 genome AF: 0.609 AC: 92621 AN: 151988 Hom.: 29023 Cov.: 31 AF XY: 0.608 AC XY: 45158 AN XY: 74278

African (AFR) AF: 0.753 AC: 31261 AN: 41488

American (AMR) AF: 0.677 AC: 10353 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1705 AN: 3464

East Asian (EAS) AF: 0.563 AC: 2906 AN: 5164

South Asian (SAS) AF: 0.567 AC: 2731 AN: 4814

European-Finnish (FIN) AF: 0.520 AC: 5483 AN: 10540

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.533 AC: 36205 AN: 67914

Other (OTH) AF: 0.600 AC: 1265 AN: 2108

Alfa AF: 0.577 Hom.: 11980

Bravo AF: 0.629

Asia WGS AF: 0.635 AC: 2204 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital disorder of glycosylation Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pontoneocerebellar hypoplasia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1051131; hg19: chr6-88221546; COSMIC: COSV65761432; COSMIC: COSV65761432;