6-136922647-C-A

Variant names:

• chr6-136922647-C-A
• rs776294794
• NM_001008783.3:c.219C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008783.3(SLC35D3):​c.219C>A​(p.Ser73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,456,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC35D3 NM_001008783.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098612696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35D3	NM_001008783.3	c.219C>A	p.Ser73Arg	missense_variant	Exon 1 of 2	ENST00000331858.5	NP_001008783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35D3	ENST00000331858.5	c.219C>A	p.Ser73Arg	missense_variant	Exon 1 of 2	1	NM_001008783.3	ENSP00000333591.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000167 AC: 4 AN: 239534 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 131198

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1456856 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724856

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000157

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ExAC AF: 0.0000166 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.219C>A (p.S73R) alteration is located in exon 1 (coding exon 1) of the SLC35D3 gene. This alteration results from a C to A substitution at nucleotide position 219, causing the serine (S) at amino acid position 73 to be replaced by an arginine (R). 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	Benign	0.098
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.045
Sift	Benign	0.24	T
Sift4G	Benign	0.25	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.50		Gain of methylation at S73 (P = 0.0214);
MVP		0.32
MPC		0.65
ClinPred		0.27	T
GERP RS		3.6
Varity_R		0.36
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs776294794; hg19: chr6-137243785;