chr9-96324157-C-T

Variant names:

• chr9-96324157-C-T
• NM_007001.3:c.765G>A

Variant summary

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

The NM_007001.3(SLC35D2):​c.765G>A​(p.Met255Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M255T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC35D2 NM_007001.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.48

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.765G>A	p.Met255Ile	missense_variant	Exon 10 of 12	ENST00000253270.13	NP_008932.2
SLC35D2	NM_001286990.2	c.501G>A	p.Met167Ile	missense_variant	Exon 7 of 9		NP_001273919.1
SLC35D2	NR_104627.2	n.842G>A		non_coding_transcript_exon_variant	Exon 10 of 13
SLC35D2-HSD17B3	NR_182427.1	n.842G>A		non_coding_transcript_exon_variant	Exon 10 of 26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35D2	ENST00000253270.13	c.765G>A	p.Met255Ile	missense_variant	Exon 10 of 12	1	NM_007001.3	ENSP00000253270.7
ENSG00000285269	ENST00000643789.1	n.366G>A		non_coding_transcript_exon_variant	Exon 6 of 22			ENSP00000494818.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461518 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727030

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.765G>A (p.M255I) alteration is located in exon 10 (coding exon 10) of the SLC35D2 gene. This alteration results from a G to A substitution at nucleotide position 765, causing the methionine (M) at amino acid position 255 to be replaced by an isoleucine (I). 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	0.73
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.64	T
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Uncertain	0.30
Sift	Benign	0.073	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.41	B;P
Vest4		0.70
MutPred		0.58		Gain of catalytic residue at M255 (P = 0.0248);.;
MVP		0.56
MPC		0.45
ClinPred		0.98	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.78

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: chr9-99086439;