17-49706221-C-T

Variant names:

• chr17-49706221-C-T
• rs748233244
• NM_005827.4:c.322G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005827.4(SLC35B1):​c.322G>A​(p.Val108Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,452,938 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V108L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC35B1 NM_005827.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89
• Publications: 0 publications found

Genes affected

SLC35B1 (HGNC:20798): (solute carrier family 35 member B1) This gene encodes a nucleotide sugar transporter which is a member of solute carrier family 35. The transporters in this family are highly conserved hydrophobic proteins with multiple transmembrane domains. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38195992).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005827.4. 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
	SLC35B1	NM_005827.4	MANE Select	c.322G>A	p.Val108Ile	missense	Exon 3 of 9	NP_005818.3	P78383-1
	SLC35B1	NM_001278784.2		c.121G>A	p.Val41Ile	missense	Exon 3 of 9	NP_001265713.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35B1	ENST00000240333.12	TSL:1 MANE Select	c.322G>A	p.Val108Ile	missense	Exon 3 of 9	ENSP00000240333.8	P78383-1
	SLC35B1	ENST00000649906.1		c.433G>A	p.Val145Ile	missense	Exon 3 of 9	ENSP00000497423.1	P78383-2
	SLC35B1	ENST00000858530.1		c.322G>A	p.Val108Ile	missense	Exon 3 of 10	ENSP00000528589.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000415 AC: 1 AN: 241170 AF XY: 0.00000766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000574

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452938 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 722770

African (AFR) AF: 0.00 AC: 0 AN: 32768

American (AMR) AF: 0.00 AC: 0 AN: 41978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25852

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 84200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109516

Other (OTH) AF: 0.00 AC: 0 AN: 59996

GnomAD4 genome Cov.: 24

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	Benign	0.15
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.71	N
PhyloP100		5.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.074
Sift	Benign	0.18	T
Sift4G	Benign	0.22	T
Polyphen		0.17	B
MutPred		0.56		Loss of helix (P = 0.1299)
MVP		0.18
MPC		0.32
ClinPred		0.55	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.41

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: rs748233244; hg19: chr17-47783583;