chr21-32412899-G-A

Variant names:

• chr21-32412899-G-A
• rs759104056
• NM_058187.5:c.46G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_058187.5(EVA1C):​c.46G>A​(p.Val16Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000858 in 1,514,416 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000081 (0 hom.)
• Consequence: EVA1C NM_058187.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07
• 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_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008935124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1C	NM_058187.5	c.46G>A	p.Val16Met	missense_variant	Exon 1 of 8	ENST00000300255.7	NP_478067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVA1C	ENST00000300255.7	c.46G>A	p.Val16Met	missense_variant	Exon 1 of 8	1	NM_058187.5	ENSP00000300255.2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000708 AC: 8 AN: 113044 AF XY: 0.0000638

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000397

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000808 AC: 11 AN: 1362208 Hom.: 0 Cov.: 31 AF XY: 0.00000744 AC XY: 5 AN XY: 671992

African (AFR) AF: 0.0000355 AC: 1 AN: 28176

American (AMR) AF: 0.000279 AC: 9 AN: 32208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24252

East Asian (EAS) AF: 0.00 AC: 0 AN: 31722

South Asian (SAS) AF: 0.00 AC: 0 AN: 76236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5510

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1066874

Other (OTH) AF: 0.0000177 AC: 1 AN: 56644

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000186 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.46G>A (p.V16M) alteration is located in exon 1 (coding exon 1) of the EVA1C gene. This alteration results from a G to A substitution at nucleotide position 46, causing the valine (V) at amino acid position 16 to be replaced by a methionine (M). 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	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0023	T;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.0089	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;.;N
PhyloP100		1.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.14	N;N;N
REVEL	Benign	0.064
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.020	D;D;D
Polyphen		0.11	B;B;.
Vest4		0.15
MutPred		0.14		Gain of glycosylation at P15 (P = 0.0685);Gain of glycosylation at P15 (P = 0.0685);Gain of glycosylation at P15 (P = 0.0685);
MVP		0.12
MPC		0.35
ClinPred		0.044	T
GERP RS		1.8
PromoterAI		0.037	Neutral
Varity_R		0.087
gMVP		0.20
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs759104056; hg19: chr21-33785207;