21-32457668-C-G

Variant names:

• chr21-32457668-C-G
• NM_058187.5:c.429C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_058187.5(EVA1C):​c.429C>G​(p.Asp143Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EVA1C NM_058187.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1C	NM_058187.5	c.429C>G	p.Asp143Glu	missense_variant	Exon 3 of 8	ENST00000300255.7	NP_478067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVA1C	ENST00000300255.7	c.429C>G	p.Asp143Glu	missense_variant	Exon 3 of 8	1	NM_058187.5	ENSP00000300255.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.429C>G (p.D143E) alteration is located in exon 3 (coding exon 3) of the EVA1C gene. This alteration results from a C to G substitution at nucleotide position 429, causing the aspartic acid (D) at amino acid position 143 to be replaced by a glutamic acid (E). 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	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;.;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.95	D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.5	M;.;M;.
PhyloP100		1.9
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Uncertain	0.018	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.72
MutPred		0.89		Gain of disorder (P = 0.173);Gain of disorder (P = 0.173);Gain of disorder (P = 0.173);.;
MVP		0.39
MPC		0.70
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.43
gMVP		0.79
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

hg19: chr21-33829976;