Variant 7-134309384-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032826.5(SLC35B4):c.173C>T(p.Pro58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,608,706 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

SLC35B4
NM_032826.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.257

Variant links:

Genes affected

SLC35B4 (HGNC:20584): (solute carrier family 35 member B4) Glycosyltransferases, such as SLC35B4, transport nucleotide sugars from the cytoplasm where they are synthesized, to the Golgi apparatus where they are utilized in the synthesis of glycoproteins, glycolipids, and proteoglycans (Ashikov et al., 2005 [PubMed 15911612]).[supplied by OMIM, Mar 2008]

SLC35B4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037760526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35B4	NM_032826.5 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	2/10	ENST00000378509.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35B4	ENST00000378509.9 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	2/10	1	NM_032826.5	P1	Q969S0-1
SLC35B4	ENST00000470969.2 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	2/8	1			Q969S0-2
SLC35B4	ENST00000416907.5 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant, NMD_transcript_variant	2/9	1

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000335

AC:

AN:

245036

Hom.:

AF XY:

0.000310

AC XY:

AN XY:

132462

show subpopulations

Gnomad AFR exome

AF:

0.000319

Gnomad AMR exome

AF:

0.000235

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000503

Gnomad NFE exome

AF:

0.000511

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000464

AC:

676

AN:

1456470

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

325

AN XY:

724376

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.000641

Gnomad4 NFE exome

AF:

0.000536

Gnomad4 OTH exome

AF:

0.000531

GnomAD4 genome

AF:

0.000348

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000420

Hom.:

Bravo

AF:

0.000291

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000313

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.173C>T (p.P58L) alteration is located in exon 2 (coding exon 2) of the SLC35B4 gene. This alteration results from a C to T substitution at nucleotide position 173, causing the proline (P) at amino acid position 58 to be replaced by a leucine (L). 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

0.090

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.0071

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

0.93

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.044

Sift

Benign

0.033

D;.

Sift4G

Benign

0.11

T;T

Polyphen

0.084

B;B

Vest4

0.19

MVP

0.59

MPC

0.29

ClinPred

0.017

GERP RS

-0.25

Varity_R

0.050

gMVP

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over