9-96383480-T-G

Variant names:

• chr9-96383480-T-G
• rs571683940
• NM_007001.3:c.155A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_007001.3(SLC35D2):​c.155A>C​(p.Tyr52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y52C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC35D2 NM_007001.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38
• 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]

SLC35D2-HSD17B3 (HGNC:):

ACMG classification

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

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

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.155A>C	p.Tyr52Ser	missense	Exon 1 of 12	NP_008932.2	Q76EJ3-1
	SLC35D2	NM_001286990.2		c.155A>C	p.Tyr52Ser	missense	Exon 1 of 9	NP_001273919.1	Q76EJ3-2
	SLC35D2	NR_104627.2		n.232A>C		non_coding_transcript_exon	Exon 1 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35D2	ENST00000253270.13	TSL:1 MANE Select	c.155A>C	p.Tyr52Ser	missense	Exon 1 of 12	ENSP00000253270.7	Q76EJ3-1
	SLC35D2	ENST00000375259.9	TSL:1	c.155A>C	p.Tyr52Ser	missense	Exon 1 of 9	ENSP00000364408.4	Q76EJ3-2
	SLC35D2	ENST00000955257.1		c.155A>C	p.Tyr52Ser	missense	Exon 1 of 13	ENSP00000625316.1

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149566 Hom.: 0 Cov.: 31

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: 0.0000298

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000109 AC: 146 AN: 1340156 Hom.: 0 Cov.: 31 AF XY: 0.000103 AC XY: 68 AN XY: 662338

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000107 AC: 3 AN: 27952

American (AMR) AF: 0.0000290 AC: 1 AN: 34500

Ashkenazi Jewish (ASJ) AF: 0.0000423 AC: 1 AN: 23626

East Asian (EAS) AF: 0.00 AC: 0 AN: 31388

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78176

European-Finnish (FIN) AF: 0.0000887 AC: 4 AN: 45100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5146

European-Non Finnish (NFE) AF: 0.000124 AC: 129 AN: 1039188

Other (OTH) AF: 0.000127 AC: 7 AN: 55080

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000134 AC: 2 AN: 149566 Hom.: 0 Cov.: 31 AF XY: 0.0000274 AC XY: 2 AN XY: 72930

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40980

American (AMR) AF: 0.00 AC: 0 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 4916

South Asian (SAS) AF: 0.00 AC: 0 AN: 4630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000298 AC: 2 AN: 67162

Other (OTH) AF: 0.00 AC: 0 AN: 2066

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	-0.069	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.56		Gain of glycosylation at Y52 (P = 0.007)
MVP		0.57
MPC		0.47
ClinPred		0.99	D
GERP RS		3.1
PromoterAI		0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.60
Mutation Taster		=48/52	disease causing

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

dbSNP: rs571683940; hg19: chr9-99145762;