dbSNP rs530160904: SLC35E4:p.Glu7Lys (chr22-30636469-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001001479.4(SLC35E4):c.19G>A(p.Glu7Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000133 in 1,501,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

SLC35E4
NM_001001479.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.524

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=0.109695554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35E4	NM_001001479.4 link	c.19G>A	p.Glu7Lys	missense_variant	Exon 1 of 2	ENST00000343605.5	NP_001001479.1	Q6ICL7-1
SLC35E4	NM_001318370.2 link	c.19G>A	p.Glu7Lys	missense_variant	Exon 1 of 3		NP_001305299.1	Q6ICL7-2
SLC35E4	NM_001318371.2 link	c.19G>A	p.Glu7Lys	missense_variant	Exon 1 of 3		NP_001305300.1	Q6ICL7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC35E4	ENST00000343605.5 link	c.19G>A	p.Glu7Lys	missense_variant	Exon 1 of 2	1	NM_001001479.4	ENSP00000339626.4	Q6ICL7-1
SLC35E4	ENST00000406566.1 link	c.19G>A	p.Glu7Lys	missense_variant	Exon 1 of 3	1		ENSP00000384377.1	Q6ICL7-2
SLC35E4	ENST00000451479.1 link	c.-54G>A		upstream_gene_variant		1		ENSP00000413552.1	H7C3S2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.41e-7

AC:

AN:

1349136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

658306

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:

9.52e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.056

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.056

Sift

Uncertain

0.013

D;D

Sift4G

Benign

0.070

T;T

Polyphen

0.037

B;.

Vest4

0.21

MutPred

0.34

Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);

MVP

0.23

MPC

0.50

ClinPred

0.85

GERP RS

4.5

Varity_R

0.10

gMVP

0.52

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over