6-87477427-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006416.5(SLC35A1):c.82A>G(p.Thr28Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35A1 NM_006416.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A1	NM_006416.5	c.82A>G	p.Thr28Ala	missense_variant	2/8	ENST00000369552.9
SLC35A1	NM_001168398.2	c.82A>G	p.Thr28Ala	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A1	ENST00000369552.9	c.82A>G	p.Thr28Ala	missense_variant	2/8	1	NM_006416.5	P1
SLC35A1	ENST00000369556.7	c.82A>G	p.Thr28Ala	missense_variant	2/7	1
SLC35A1	ENST00000369557.9	c.82A>G	p.Thr28Ala	missense_variant	2/6	2
SLC35A1	ENST00000464978.5	n.157A>G		non_coding_transcript_exon_variant	2/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.82A>G (p.T28A) alteration is located in exon 2 (coding exon 2) of the SLC35A1 gene. This alteration results from a A to G substitution at nucleotide position 82, causing the threonine (T) at amino acid position 28 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.0083	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	21
Dann	Uncertain	0.98
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M;.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.58	N;N;N;.
REVEL	Benign	0.19
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.17	.;.;B;.
Vest4		0.63
MutPred		0.54		Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);.;
MVP		0.58
MPC		0.33
ClinPred		0.92	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.14
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-88187145;