9-96383498-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_007001.3(SLC35D2):ā€‹c.137A>Gā€‹(p.Lys46Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,536,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)
Exomes š‘“: 7.2e-7 ( 0 hom. )

Consequence

SLC35D2
NM_007001.3 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.35
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC35D2NM_007001.3 linkc.137A>G p.Lys46Arg missense_variant 1/12 ENST00000253270.13 NP_008932.2 Q76EJ3-1A0A024R9N5
SLC35D2NM_001286990.2 linkc.137A>G p.Lys46Arg missense_variant 1/9 NP_001273919.1 Q76EJ3-2
SLC35D2NR_104627.2 linkn.214A>G non_coding_transcript_exon_variant 1/13
SLC35D2-HSD17B3NR_182427.1 linkn.214A>G non_coding_transcript_exon_variant 1/26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC35D2ENST00000253270.13 linkc.137A>G p.Lys46Arg missense_variant 1/121 NM_007001.3 ENSP00000253270.7 Q76EJ3-1
SLC35D2ENST00000375259.9 linkc.137A>G p.Lys46Arg missense_variant 1/91 ENSP00000364408.4 Q76EJ3-2
SLC35D2ENST00000375257.2 linkc.137A>G p.Lys46Arg missense_variant 1/62 ENSP00000364406.1 Q5VZJ2
SLC35D2ENST00000482643.2 linkn.183A>G non_coding_transcript_exon_variant 1/95

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151790
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.22e-7
AC:
1
AN:
1384336
Hom.:
0
Cov.:
31
AF XY:
0.00000146
AC XY:
1
AN XY:
683442
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.0000175
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151790
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74120
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000191
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 07, 2023The c.137A>G (p.K46R) alteration is located in exon 1 (coding exon 1) of the SLC35D2 gene. This alteration results from a A to G substitution at nucleotide position 137, causing the lysine (K) at amino acid position 46 to be replaced by an arginine (R). 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
0.34
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.20
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
T;.;.
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Pathogenic
0.97
D
MetaRNN
Pathogenic
0.78
D;D;D
MetaSVM
Uncertain
0.79
D
MutationAssessor
Pathogenic
3.3
M;M;.
PrimateAI
Pathogenic
0.80
D
PROVEAN
Uncertain
-2.5
D;N;D
REVEL
Pathogenic
0.79
Sift
Uncertain
0.029
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.50
MutPred
0.57
Loss of methylation at K46 (P = 0.0091);Loss of methylation at K46 (P = 0.0091);Loss of methylation at K46 (P = 0.0091);
MVP
0.79
MPC
0.44
ClinPred
0.99
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.70
gMVP
0.76

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs762591752; hg19: chr9-99145780; API