9-96360215-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_007001.3(SLC35D2):​c.286C>G​(p.Pro96Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SLC35D2
NM_007001.3 missense

Scores

8
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.18
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC35D2NM_007001.3 linkc.286C>G p.Pro96Ala missense_variant 4/12 ENST00000253270.13 NP_008932.2 Q76EJ3-1A0A024R9N5
SLC35D2NM_001286990.2 linkc.286C>G p.Pro96Ala missense_variant 4/9 NP_001273919.1 Q76EJ3-2
SLC35D2NR_104627.2 linkn.363C>G non_coding_transcript_exon_variant 4/13
SLC35D2-HSD17B3NR_182427.1 linkn.363C>G non_coding_transcript_exon_variant 4/26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC35D2ENST00000253270.13 linkc.286C>G p.Pro96Ala missense_variant 4/121 NM_007001.3 ENSP00000253270.7 Q76EJ3-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
31

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 GeneticsMar 25, 2024The c.286C>G (p.P96A) alteration is located in exon 4 (coding exon 4) of the SLC35D2 gene. This alteration results from a C to G substitution at nucleotide position 286, causing the proline (P) at amino acid position 96 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
Pathogenic
0.72
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T;.;.
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.095
D
MetaRNN
Pathogenic
0.85
D;D;D
MetaSVM
Uncertain
0.35
D
MutationAssessor
Pathogenic
3.1
M;M;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-7.5
D;D;D
REVEL
Uncertain
0.57
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.82
MutPred
0.54
Gain of catalytic residue at P96 (P = 0.0609);Gain of catalytic residue at P96 (P = 0.0609);Gain of catalytic residue at P96 (P = 0.0609);
MVP
0.73
MPC
0.69
ClinPred
1.0
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.72
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr9-99122497; API