21-32453418-T-G

Variant names:

• chr21-32453418-T-G
• NM_058187.5:c.267T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_058187.5(EVA1C):​c.267T>G​(p.Phe89Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.922
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1C	NM_058187.5	c.267T>G	p.Phe89Leu	missense_variant	Exon 2 of 8	ENST00000300255.7	NP_478067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVA1C	ENST00000300255.7	c.267T>G	p.Phe89Leu	missense_variant	Exon 2 of 8	1	NM_058187.5	ENSP00000300255.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.267T>G (p.F89L) alteration is located in exon 2 (coding exon 2) of the EVA1C gene. This alteration results from a T to G substitution at nucleotide position 267, causing the phenylalanine (F) at amino acid position 89 to be replaced by a leucine (L). 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	0.94
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;T;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;L
PhyloP100		0.92
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.54
MutPred		0.48		Gain of disorder (P = 0.1208);Gain of disorder (P = 0.1208);Gain of disorder (P = 0.1208);
MVP		0.22
MPC		1.0
ClinPred		0.95	D
GERP RS		2.4
Varity_R		0.49
gMVP		0.62
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr21-33825726;