Genetic Variant EVA1C:p.Lys44Arg (chr21-32412984-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_058187.5(EVA1C):c.131A>G(p.Lys44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000336 in 1,487,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. K44I) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

EVA1C
NM_058187.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.424

Publications

0 publications found

Variant links:

Genes affected

EVA1C (HGNC:13239): (eva-1 homolog C) Enables heparin binding activity. Colocalizes with extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

EVA1C links:

CFAP298-TCP10L (HGNC:54636): (CFAP298-TCP10L readthrough) This locus represents naturally occurring readthrough transcription between the neighboring chromosome 21 open reading frame 59 (C21orf59) and TCP10L (t-complex 10 like) genes on chromosome 21. Readthrough transcripts may encode a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

CFAP298-TCP10L links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054863423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1C	NM_058187.5 link	c.131A>G	p.Lys44Arg	missense_variant	Exon 1 of 8	ENST00000300255.7	NP_478067.2	P58658-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVA1C	ENST00000300255.7 link	c.131A>G	p.Lys44Arg	missense_variant	Exon 1 of 8	1	NM_058187.5	ENSP00000300255.2		P58658-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152124

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000299

AC:

AN:

1335754

Hom.:

Cov.:

AF XY:

0.00000457

AC XY:

AN XY:

656230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27480

American (AMR)

AF:

0.00

AC:

AN:

28104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22284

East Asian (EAS)

AF:

0.00

AC:

AN:

31788

South Asian (SAS)

AF:

0.0000567

AC:

AN:

70542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5336

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1045864

Other (OTH)

AF:

0.00

AC:

AN:

54414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2094

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.9

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0077

T;T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.32

N;.;N

PhyloP100

-0.42

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.77

N;N;N

REVEL

Benign

0.043

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.092

MutPred

0.43

Loss of ubiquitination at K44 (P = 0.013);Loss of ubiquitination at K44 (P = 0.013);Loss of ubiquitination at K44 (P = 0.013);

MVP

0.11

MPC

0.24

ClinPred

0.095

GERP RS

-2.3

PromoterAI

-0.077

Neutral

(source)

Varity_R

0.055

gMVP

0.26

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

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21-32412984-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over