9-96336761-C-A

Variant names:

• chr9-96336761-C-A
• rs772420947
• NM_007001.3:c.708G>T

Variant summary

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

The NM_007001.3(SLC35D2):​c.708G>T​(p.Lys236Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000838 in 1,431,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: SLC35D2 NM_007001.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

Genes affected

SLC35D2 (HGNC:20799): (solute carrier family 35 member D2) Nucleotide sugars, which are synthesized in the cytosol or the nucleus, are high-energy donor substrates for glycosyltransferases located in the lumen of the endoplasmic reticulum and Golgi apparatus. Translocation of nucleotide sugars from the cytosol into the lumen compartment is mediated by specific nucleotide sugar transporters, such as SLC35D2 (Suda et al., 2004 [PubMed 15082721]).[supplied by OMIM, Mar 2008]

ENSG00000285269 (HGNC:):

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 rank	MANE	Protein	UniProt
SLC35D2	NM_007001.3	c.708G>T	p.Lys236Asn	missense_variant	Exon 9 of 12	ENST00000253270.13	NP_008932.2
SLC35D2	NM_001286990.2	c.489-12592G>T		intron_variant	Intron 6 of 8		NP_001273919.1
SLC35D2	NR_104627.2	n.785G>T		non_coding_transcript_exon_variant	Exon 9 of 13
SLC35D2-HSD17B3	NR_182427.1	n.785G>T		non_coding_transcript_exon_variant	Exon 9 of 26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35D2	ENST00000253270.13	c.708G>T	p.Lys236Asn	missense_variant	Exon 9 of 12	1	NM_007001.3	ENSP00000253270.7
ENSG00000285269	ENST00000643789.1	n.309G>T		non_coding_transcript_exon_variant	Exon 5 of 22			ENSP00000494818.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000838 AC: 12 AN: 1431788 Hom.: 0 Cov.: 27 AF XY: 0.00000703 AC XY: 5 AN XY: 711078

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000232

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ExAC AF: 0.0000166 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.708G>T (p.K236N) alteration is located in exon 9 (coding exon 9) of the SLC35D2 gene. This alteration results from a G to T substitution at nucleotide position 708, causing the lysine (K) at amino acid position 236 to be replaced by an asparagine (N). 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	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.091
Sift	Benign	0.57	T
Sift4G	Benign	0.60	T
Polyphen		0.0040	B
Vest4		0.44
MutPred		0.63		Loss of methylation at K236 (P = 0.0022);
MVP		0.26
MPC		0.35
ClinPred		0.21	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.49		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.49		Position offset: 23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs772420947; hg19: chr9-99099043;