6-87473010-G-C

Variant names:

• chr6-87473010-G-C
• rs149903512
• NM_006416.5:c.7G>C

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.7G>C​(p.Ala3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC35A1 NM_006416.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 2 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 (MetaRNN=0.056029856).

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.7G>C	p.Ala3Pro	missense	Exon 1 of 8	NP_006407.1	P78382-1
	SLC35A1	NM_001168398.2		c.7G>C	p.Ala3Pro	missense	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.7G>C	p.Ala3Pro	missense	Exon 1 of 8	ENSP00000358565.4	P78382-1
	SLC35A1	ENST00000369556.7	TSL:1	c.7G>C	p.Ala3Pro	missense	Exon 1 of 7	ENSP00000358569.3	P78382-2
	ENSG00000213204	ENST00000507897.5	TSL:2	n.*61-4352G>C		intron	N/A	ENSP00000426769.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 15946 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 529850 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 270434

African (AFR) AF: 0.00 AC: 0 AN: 11368

American (AMR) AF: 0.00 AC: 0 AN: 8774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12070

East Asian (EAS) AF: 0.00 AC: 0 AN: 24536

South Asian (SAS) AF: 0.00 AC: 0 AN: 30696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 383110

Other (OTH) AF: 0.00 AC: 0 AN: 26222

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74374

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

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.14
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.047
Sift	Benign	0.26	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.27		Loss of stability (P = 0.0181)
MVP		0.30
MPC		0.44
ClinPred		0.092	T
GERP RS		2.2
PromoterAI		-0.49	Neutral
Varity_R		0.17
gMVP		0.50
Mutation Taster		=93/7	polymorphism

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: rs149903512; hg19: chr6-88182728;