6-87477213-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006416.5(SLC35A1):​c.17-149C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 496,530 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: SLC35A1 NM_006416.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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>A		intron	N/A	NP_006407.1	P78382-1
	SLC35A1	NM_001168398.2		c.17-149C>A		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>A		intron	N/A	ENSP00000358565.4	P78382-1
	SLC35A1	ENST00000369556.7	TSL:1	c.17-149C>A		intron	N/A	ENSP00000358569.3	P78382-2
	ENSG00000213204	ENST00000507897.5	TSL:2	n.*61-149C>A		intron	N/A	ENSP00000426769.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000201 AC: 1 AN: 496530 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 263954

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13420

American (AMR) AF: 0.00 AC: 0 AN: 25554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15146

East Asian (EAS) AF: 0.00 AC: 0 AN: 29378

South Asian (SAS) AF: 0.00 AC: 0 AN: 50072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2024

European-Non Finnish (NFE) AF: 0.00000326 AC: 1 AN: 306734

Other (OTH) AF: 0.00 AC: 0 AN: 27132

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.20
DANN	Benign	0.38
PhyloP100		-0.58

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;