Genetic Variant NM_058187.5:c.628C>A (chr21-32467842-C-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_058187.5(EVA1C):c.628C>A(p.Pro210Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000398 in 1,607,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P210A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000041 ( 0 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: 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=0.2193205).

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>A	p.Pro210Thr	missense	Exon 4 of 8	NP_478067.2
EVA1C	NM_001286556.2		c.628C>A	p.Pro210Thr	missense	Exon 4 of 8	NP_001273485.1	P58658-3
EVA1C	NM_001320745.2		c.343C>A	p.Pro115Thr	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>A	p.Pro210Thr	missense	Exon 4 of 8	ENSP00000300255.2	P58658-1
EVA1C	ENST00000382699.7	TSL:1	c.628C>A	p.Pro210Thr	missense	Exon 4 of 8	ENSP00000372146.3	P58658-3
EVA1C	ENST00000437338.5	TSL:1	n.*218C>A		non_coding_transcript_exon	Exon 3 of 7	ENSP00000389291.1	A0A0C4DG64

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000533

AC:

AN:

244102

AF XY:

0.0000529

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000921

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000226

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000405

AC:

AN:

1455978

Hom.:

Cov.:

AF XY:

0.0000387

AC XY:

AN XY:

724338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33084

American (AMR)

AF:

0.0000917

AC:

AN:

43598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25910

East Asian (EAS)

AF:

0.000127

AC:

AN:

39250

South Asian (SAS)

AF:

0.0000704

AC:

AN:

85252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

1109700

Other (OTH)

AF:

0.0000333

AC:

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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:

0.0000329

AC:

AN:

151822

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41264

American (AMR)

AF:

0.00

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2086

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

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:

0.0000502

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000247

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

0.078

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0099

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.018

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

PhyloP100

5.3

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.15

Sift

Benign

0.073

Sift4G

Benign

0.062

Polyphen

0.99

Vest4

0.47

MVP

0.37

MPC

0.98

ClinPred

0.22

GERP RS

5.6

Varity_R

0.15

gMVP

0.63

Mutation Taster

=57/43

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