Genetic Variant EVA1C:p.Pro210Ala (chr21-32467842-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_058187.5(EVA1C):c.628C>G(p.Pro210Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000165 in 1,607,910 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P210T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 4 hom. )

Consequence

EVA1C
NM_058187.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038518548).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058187.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVA1C	NM_058187.5	MANE Select	c.628C>G	p.Pro210Ala	missense	Exon 4 of 8	NP_478067.2
EVA1C	NM_001286556.2		c.628C>G	p.Pro210Ala	missense	Exon 4 of 8	NP_001273485.1	P58658-3
EVA1C	NM_001320745.2		c.343C>G	p.Pro115Ala	missense	Exon 4 of 8	NP_001307674.1	B3KWG0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVA1C	ENST00000300255.7	TSL:1 MANE Select	c.628C>G	p.Pro210Ala	missense	Exon 4 of 8	ENSP00000300255.2	P58658-1
EVA1C	ENST00000382699.7	TSL:1	c.628C>G	p.Pro210Ala	missense	Exon 4 of 8	ENSP00000372146.3	P58658-3
EVA1C	ENST00000437338.5	TSL:1	n.*218C>G		non_coding_transcript_exon	Exon 3 of 7	ENSP00000389291.1	A0A0C4DG64

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000395

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000361

AC:

AN:

244102

AF XY:

0.000378

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000921

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000144

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1455970

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

155

AN XY:

724330

show subpopulations

African (AFR)

AF:

0.0000907

AC:

AN:

33084

American (AMR)

AF:

0.000780

AC:

AN:

43596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25910

East Asian (EAS)

AF:

0.000102

AC:

AN:

39250

South Asian (SAS)

AF:

0.00145

AC:

124

AN:

85248

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00192

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000622

AC:

AN:

1109698

Other (OTH)

AF:

0.000116

AC:

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000724

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41386

American (AMR)

AF:

0.000394

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.000416

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.000346

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0093

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

M_CAP

Benign

0.015

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

5.3

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.11

Sift

Benign

0.11

Sift4G

Benign

0.062

Polyphen

0.96

Vest4

0.39

MVP

0.36

MPC

0.73

ClinPred

0.073

GERP RS

5.6

Varity_R

0.072

gMVP

0.55

Mutation Taster

=61/39

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over