6-87472986-G-C

Variant names:

• chr6-87472986-G-C
• rs9450704
• NM_006416.5:c.-18G>C

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.-18G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 657,550 control chromosomes in the GnomAD database, including 101,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (30014 hom., cov: 34)
  • Exomes 𝑓: 0.52 (71271 hom.)
• Consequence: SLC35A1 NM_006416.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.620
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-87472986-G-C is Benign according to our data. Variant chr6-87472986-G-C is described in ClinVar as Benign. ClinVar VariationId is 95391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 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.-18G>C		5_prime_UTR	Exon 1 of 8	NP_006407.1	P78382-1
	SLC35A1	NM_001168398.2		c.-18G>C		5_prime_UTR	Exon 1 of 7	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.-18G>C		5_prime_UTR	Exon 1 of 8	ENSP00000358565.4	P78382-1
	SLC35A1	ENST00000369556.7	TSL:1	c.-18G>C		5_prime_UTR	Exon 1 of 7	ENSP00000358569.3	P78382-2
	ENSG00000213204	ENST00000507897.5	TSL:2	n.*61-4376G>C		intron	N/A	ENSP00000426769.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93553 AN: 152000 Hom.: 29958 Cov.: 34

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.603

GnomAD2 exomes AF: 0.598 AC: 7759 AN: 12976 AF XY: 0.582

Gnomad AFR exome AF: 0.826

Gnomad AMR exome AF: 0.699

Gnomad ASJ exome AF: 0.514

Gnomad EAS exome AF: 0.520

Gnomad FIN exome AF: 0.606

Gnomad NFE exome AF: 0.561

Gnomad OTH exome AF: 0.554

GnomAD4 exome AF: 0.525 AC: 265277 AN: 505432 Hom.: 71271 Cov.: 7 AF XY: 0.525 AC XY: 137165 AN XY: 261452

African (AFR) AF: 0.786 AC: 8554 AN: 10882

American (AMR) AF: 0.693 AC: 6363 AN: 9188

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 5884 AN: 12270

East Asian (EAS) AF: 0.513 AC: 12551 AN: 24484

South Asian (SAS) AF: 0.540 AC: 17598 AN: 32580

European-Finnish (FIN) AF: 0.500 AC: 14058 AN: 28128

Middle Eastern (MID) AF: 0.550 AC: 1787 AN: 3250

European-Non Finnish (NFE) AF: 0.513 AC: 184339 AN: 359016

Other (OTH) AF: 0.552 AC: 14143 AN: 25634

GnomAD4 genome AF: 0.616 AC: 93671 AN: 152118 Hom.: 30014 Cov.: 34 AF XY: 0.613 AC XY: 45548 AN XY: 74358

African (AFR) AF: 0.793 AC: 32947 AN: 41548

American (AMR) AF: 0.682 AC: 10419 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1705 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2617 AN: 5132

South Asian (SAS) AF: 0.563 AC: 2716 AN: 4828

European-Finnish (FIN) AF: 0.481 AC: 5099 AN: 10602

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36176 AN: 67940

Other (OTH) AF: 0.606 AC: 1277 AN: 2108

Alfa AF: 0.439 Hom.: 1175

Bravo AF: 0.641

Asia WGS AF: 0.615 AC: 2135 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	SLC35A1-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.62
PromoterAI		0.38	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs9450704; hg19: chr6-88182704; COSMIC: COSV65780209; COSMIC: COSV65780209;