rs114156788

chr6-87477364-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006416.5(SLC35A1):c.19A>C(p.Asn7His) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00107 in 1,612,270 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (7 hom.)
• Consequence: SLC35A1 NM_006416.5 missense, splice_region
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.98

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004863143).
• BP6: Variant 6-87477364-A-C is Benign according to our data. Variant chr6-87477364-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 95392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00575 (876/152290) while in subpopulation AFR AF= 0.0195 (810/41542). AF 95% confidence interval is 0.0184. There are 2 homozygotes in gnomad4. There are 403 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A1	NM_006416.5	c.19A>C	p.Asn7His	missense_variant, splice_region_variant	2/8	ENST00000369552.9
SLC35A1	NM_001168398.2	c.19A>C	p.Asn7His	missense_variant, splice_region_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A1	ENST00000369552.9	c.19A>C	p.Asn7His	missense_variant, splice_region_variant	2/8	1	NM_006416.5	P1
SLC35A1	ENST00000369556.7	c.19A>C	p.Asn7His	missense_variant, splice_region_variant	2/7	1
SLC35A1	ENST00000369557.9	c.19A>C	p.Asn7His	missense_variant, splice_region_variant	2/6	2
SLC35A1	ENST00000464978.5	n.94A>C		splice_region_variant, non_coding_transcript_exon_variant	2/7	2

Frequencies

GnomAD3 genomes AF: 0.00570 AC: 868 AN: 152172 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00144 AC: 360 AN: 250156 Hom.: 4 AF XY: 0.00103 AC XY: 140 AN XY: 135306

Gnomad AFR exome AF: 0.0196

Gnomad AMR exome AF: 0.000897

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000586 AC: 855 AN: 1459980 Hom.: 7 Cov.: 31 AF XY: 0.000519 AC XY: 377 AN XY: 726368

Gnomad4 AFR exome AF: 0.0211

Gnomad4 AMR exome AF: 0.000961

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00575 AC: 876 AN: 152290 Hom.: 2 Cov.: 32 AF XY: 0.00541 AC XY: 403 AN XY: 74470

Gnomad4 AFR AF: 0.0195

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.00670

ESP6500AA AF: 0.0154 AC: 68

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00185 AC: 225

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 06, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 22, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

SLC35A1-congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

SLC35A1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 06, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Oct 11, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T;T;T
MetaRNN	Benign	0.0049	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.091
Sift	Uncertain	0.011	D;D;D
Sift4G	Uncertain	0.035	D;D;D
Polyphen		0.96	.;.;D
Vest4		0.39
MVP		0.63
MPC		0.68
ClinPred		0.027	T
GERP RS		5.6
Varity_R		0.14
gMVP		0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs114156788; hg19: chr6-88187082;