Variant chr22-30636593-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001479.4(SLC35E4):c.143G>A(p.Arg48Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,452,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SLC35E4
NM_001001479.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.403

Variant links:

Genes affected

SLC35E4 (HGNC:17058): (solute carrier family 35 member E4) Predicted to enable antiporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

SLC35E4 links:

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ACMG classification

Classification made for transcript

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=0.19722521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC35E4	NM_001001479.4 linkuse as main transcript	c.143G>A	p.Arg48Gln	missense_variant	1/2	ENST00000343605.5
SLC35E4	NM_001318370.2 linkuse as main transcript	c.143G>A	p.Arg48Gln	missense_variant	1/3
SLC35E4	NM_001318371.2 linkuse as main transcript	c.143G>A	p.Arg48Gln	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35E4	ENST00000343605.5 linkuse as main transcript	c.143G>A	p.Arg48Gln	missense_variant	1/2	1	NM_001001479.4	P1	Q6ICL7-1
SLC35E4	ENST00000406566.1 linkuse as main transcript	c.143G>A	p.Arg48Gln	missense_variant	1/3	1			Q6ICL7-2
SLC35E4	ENST00000451479.1 linkuse as main transcript	c.71G>A	p.Arg24Gln	missense_variant	1/3	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000878

AC:

AN:

227780

Hom.:

AF XY:

0.00000796

AC XY:

AN XY:

125616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000201

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1452382

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721872

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:

0.00000632

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

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

Dec 21, 2022

The c.143G>A (p.R48Q) alteration is located in exon 1 (coding exon 1) of the SLC35E4 gene. This alteration results from a G to A substitution at nucleotide position 143, causing the arginine (R) at amino acid position 48 to be replaced by a glutamine (Q). 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

0.089

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.017

T;.;.

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M;.

MutationTaster

Benign

0.81

N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.38

N;N;N

REVEL

Benign

0.092

Sift

Benign

0.057

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.97

D;P;.

Vest4

0.050

MutPred

0.52

Loss of methylation at R48 (P = 0.0118);Loss of methylation at R48 (P = 0.0118);.;

MVP

0.25

MPC

0.43

ClinPred

0.71

GERP RS

4.6

Varity_R

0.081

gMVP

0.32

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