6-136924429-C-G

Variant names:

• chr6-136924429-C-G
• rs116512494
• NM_001008783.3:c.984C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001008783.3(SLC35D3):​c.984C>G​(p.Asp328Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: SLC35D3 NM_001008783.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.691
• Publications: 3 publications found

Genes affected

SLC35D3 (HGNC:15621): (solute carrier family 35 member D3) Predicted to enable antiporter activity and pyrimidine nucleotide-sugar transmembrane transporter activity. Predicted to be involved in carbohydrate transport and pyrimidine nucleotide-sugar transmembrane transport. Predicted to act upstream of or within energy homeostasis and positive regulation of protein exit from endoplasmic reticulum. Predicted to be located in early endosome and endoplasmic reticulum. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0440045).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008783.3. 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
	SLC35D3	NM_001008783.3	MANE Select	c.984C>G	p.Asp328Glu	missense	Exon 2 of 2	NP_001008783.1	Q5M8T2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35D3	ENST00000331858.5	TSL:1 MANE Select	c.984C>G	p.Asp328Glu	missense	Exon 2 of 2	ENSP00000333591.4	Q5M8T2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 32

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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250330 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461602 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727100

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74442

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.69
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.14
Sift	Benign	0.052	T
Sift4G	Benign	0.55	T
Polyphen		0.0010	B
Vest4		0.066
MutPred		0.18		Loss of glycosylation at S326 (P = 0.2128)
MVP		0.20
MPC		0.54
ClinPred		0.055	T
GERP RS		0.30
Varity_R		0.069
gMVP		0.18
Mutation Taster		=100/0	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

dbSNP: rs116512494; hg19: chr6-137245567;