Variant 7-134294863-A-T 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.966T>A(p.Ser322Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC35B4
NM_032826.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.526

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=0.042294532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35B4	NM_032826.5 linkuse as main transcript	c.966T>A	p.Ser322Arg	missense_variant	10/10	ENST00000378509.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35B4	ENST00000378509.9 linkuse as main transcript	c.966T>A	p.Ser322Arg	missense_variant	10/10	1	NM_032826.5	P1	Q969S0-1
SLC35B4	ENST00000416907.5 linkuse as main transcript	c.*517T>A		3_prime_UTR_variant, NMD_transcript_variant	9/9	1
SLC35B4	ENST00000466599.1 linkuse as main transcript	n.197T>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Jul 14, 2021

The c.966T>A (p.S322R) alteration is located in exon 10 (coding exon 10) of the SLC35B4 gene. This alteration results from a T to A substitution at nucleotide position 966, causing the serine (S) at amino acid position 322 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

0.077

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

Cadd

Benign

9.2

Dann

Benign

0.33

DEOGEN2

Benign

0.013

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.59

M_CAP

Benign

0.0041

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.30

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

0.16

REVEL

Benign

0.021

Sift

Benign

0.59

Sift4G

Benign

0.57

Polyphen

0.0

Vest4

0.057

MutPred

0.25

Loss of ubiquitination at K321 (P = 0.0413);

MVP

0.072

MPC

0.28

ClinPred

0.0038

GERP RS

-3.6

Varity_R

0.031

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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