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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E7Q) has been classified as Uncertain significance.

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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.109695554).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001479.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC35E4	NM_001001479.4	MANE Select	c.19G>A	p.Glu7Lys	missense	Exon 1 of 2	NP_001001479.1	Q6ICL7-1
SLC35E4	NM_001318370.2		c.19G>A	p.Glu7Lys	missense	Exon 1 of 3	NP_001305299.1	Q6ICL7-2
SLC35E4	NM_001318371.2		c.19G>A	p.Glu7Lys	missense	Exon 1 of 3	NP_001305300.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC35E4	ENST00000343605.5	TSL:1 MANE Select	c.19G>A	p.Glu7Lys	missense	Exon 1 of 2	ENSP00000339626.4	Q6ICL7-1
SLC35E4	ENST00000406566.1	TSL:1	c.19G>A	p.Glu7Lys	missense	Exon 1 of 3	ENSP00000384377.1	Q6ICL7-2
SLC35E4	ENST00000451479.1	TSL:1	c.-54G>A		upstream_gene	N/A	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

African (AFR)

AF:

0.00

AC:

AN:

30462

American (AMR)

AF:

0.00

AC:

AN:

31020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22490

East Asian (EAS)

AF:

0.00

AC:

AN:

35052

South Asian (SAS)

AF:

0.00

AC:

AN:

74152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45886

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4394

European-Non Finnish (NFE)

AF:

9.52e-7

AC:

AN:

1050106

Other (OTH)

AF:

0.00

AC:

AN:

55574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Benign

-0.056

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.76

M_CAP

Benign

0.0060

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

PhyloP100

0.52

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.26

REVEL

Benign

0.056

Sift

Uncertain

0.013

Sift4G

Benign

0.070

Polyphen

0.037

Vest4

0.21

MutPred

0.34

Gain of MoRF binding (P = 0.0026)

MVP

0.23

MPC

0.50

ClinPred

0.85

GERP RS

4.5

PromoterAI

-0.069

Neutral

(source)

Varity_R

0.10

gMVP

0.52

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over