21-32457651-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_058187.5(EVA1C):​c.412C>T​(p.Arg138Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

EVA1C
NM_058187.5 missense

Scores

6
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.36
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EVA1CNM_058187.5 linkuse as main transcriptc.412C>T p.Arg138Cys missense_variant 3/8 ENST00000300255.7 NP_478067.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EVA1CENST00000300255.7 linkuse as main transcriptc.412C>T p.Arg138Cys missense_variant 3/81 NM_058187.5 ENSP00000300255 P3P58658-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251484
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461820
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 27, 2022The c.412C>T (p.R138C) alteration is located in exon 3 (coding exon 3) of the EVA1C gene. This alteration results from a C to T substitution at nucleotide position 412, causing the arginine (R) at amino acid position 138 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.61
BayesDel_addAF
Benign
-0.047
T
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.046
T;T;.;.
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Benign
0.040
D
MetaRNN
Uncertain
0.74
D;D;D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.8
M;.;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Pathogenic
-5.0
D;D;D;D
REVEL
Uncertain
0.44
Sift
Uncertain
0.0040
D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D
Polyphen
1.0
D;D;.;.
Vest4
0.55
MutPred
0.56
Loss of solvent accessibility (P = 0.1077);Loss of solvent accessibility (P = 0.1077);Loss of solvent accessibility (P = 0.1077);.;
MVP
0.36
MPC
1.2
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.46
gMVP
0.56

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.

Other links and lift over

dbSNP: rs200043057; hg19: chr21-33829959; API