9-96360215-G-C

Position:

• chr9-96360215-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.18

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]

SLC35D2-HSD17B3 (HGNC:):

ACMG classification

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
SLC35D2	NM_007001.3	c.286C>G	p.Pro96Ala	missense_variant	4/12	ENST00000253270.13	NP_008932.2
SLC35D2	NM_001286990.2	c.286C>G	p.Pro96Ala	missense_variant	4/9		NP_001273919.1
SLC35D2	NR_104627.2	n.363C>G		non_coding_transcript_exon_variant	4/13
SLC35D2-HSD17B3	NR_182427.1	n.363C>G		non_coding_transcript_exon_variant	4/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35D2	ENST00000253270.13	c.286C>G	p.Pro96Ala	missense_variant	4/12	1	NM_007001.3	ENSP00000253270.7

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The 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;