9-96324157-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007001.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35D2	NM_007001.3	MANE Select	c.765G>A	p.Met255Ile	missense	Exon 10 of 12	NP_008932.2	Q76EJ3-1
	SLC35D2	NM_001286990.2		c.501G>A	p.Met167Ile	missense	Exon 7 of 9	NP_001273919.1	Q76EJ3-2
	SLC35D2	NR_104627.2		n.842G>A		non_coding_transcript_exon	Exon 10 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35D2	ENST00000253270.13	TSL:1 MANE Select	c.765G>A	p.Met255Ile	missense	Exon 10 of 12	ENSP00000253270.7	Q76EJ3-1
	SLC35D2	ENST00000375259.9	TSL:1	c.501G>A	p.Met167Ile	missense	Exon 7 of 9	ENSP00000364408.4	Q76EJ3-2
	ENSG00000285269	ENST00000643789.1		n.366G>A		non_coding_transcript_exon	Exon 6 of 22	ENSP00000494818.1	A0A2R8Y5X9

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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111746

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.64	T
PhyloP100		4.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.30
Sift	Benign	0.073	T
Sift4G	Benign	0.14	T
Polyphen		0.41	B
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
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

hg19: chr9-99086439;