chr6-8413584-C-T

Variant names:

• chr6-8413584-C-T
• rs749208348
• NM_001370479.2:c.1075G>A

Variant summary

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

The NM_001370479.2(SLC35B3):​c.1075G>A​(p.Ala359Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,609,722 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: SLC35B3 NM_001370479.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.477
• Publications: 0 publications found

Genes affected

SLC35B3 (HGNC:21601): (solute carrier family 35 member B3) This gene is a member of the solute carrier family. The encoded protein is involved in the transport of 3-prime phosphoadenosine 5-prime phosphosulfate (PAPS) from the nucleus or the cytosol to the Golgi lumen. This gene has been reported to be expressed preferentially in the human colon tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ENSG00000285216 (HGNC:):

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=0.038218975).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370479.2. 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
	SLC35B3	NM_001370479.2	MANE Select	c.1075G>A	p.Ala359Thr	missense	Exon 10 of 10	NP_001357408.1	A0A024QZW4
	SLC35B3	NM_001142540.2		c.1171G>A	p.Ala391Thr	missense	Exon 11 of 11	NP_001136012.1	Q9H1N7-1
	SLC35B3	NM_001142541.3		c.1171G>A	p.Ala391Thr	missense	Exon 11 of 11	NP_001136013.1	Q9H1N7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35B3	ENST00000710437.1	MANE Select	c.1075G>A	p.Ala359Thr	missense	Exon 10 of 10	ENSP00000518269.1	A0A024QZW4
	SLC35B3	ENST00000379660.4	TSL:1	c.1171G>A	p.Ala391Thr	missense	Exon 11 of 11	ENSP00000368981.4	Q9H1N7-1
	SLC35B3	ENST00000644923.2		c.1171G>A	p.Ala391Thr	missense	Exon 11 of 11	ENSP00000496368.1	Q9H1N7-1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000202 AC: 5 AN: 247582 AF XY: 0.0000299

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000358

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000213 AC: 31 AN: 1457548 Hom.: 0 Cov.: 29 AF XY: 0.0000276 AC XY: 20 AN XY: 725032

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.0000225 AC: 1 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 85876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4916

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1110416

Other (OTH) AF: 0.0000166 AC: 1 AN: 60130

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

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

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	0.065
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.5
DANN	Benign	0.84
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.48
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.12
Sift	Benign	0.55	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.028
MutPred		0.24		Gain of phosphorylation at A391 (P = 0.04)
MVP		0.22
MPC		0.094
ClinPred		0.024	T
GERP RS		0.42
Varity_R		0.019
gMVP		0.55
Mutation Taster		=98/2	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: rs749208348; hg19: chr6-8413817;