21-32412920-C-T

Variant names:

• chr21-32412920-C-T
• rs146014823
• NM_058187.5:c.67C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_058187.5(EVA1C):​c.67C>T​(p.Arg23Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000189 in 1,373,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: EVA1C NM_058187.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20330948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1C	NM_058187.5	c.67C>T	p.Arg23Trp	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.67C>T	p.Arg23Trp	missense_variant	Exon 1 of 8	1	NM_058187.5	ENSP00000300255.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000189 AC: 26 AN: 1373724 Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 14 AN XY: 678376

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000196

Gnomad4 OTH exome AF: 0.0000877

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000859 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0086	T;T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.;M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.43
MutPred		0.41		Loss of disorder (P = 0.0064);Loss of disorder (P = 0.0064);Loss of disorder (P = 0.0064);
MVP		0.18
MPC		1.0
ClinPred		0.86	D
GERP RS		-1.6
Varity_R		0.17
gMVP		0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs146014823; hg19: chr21-33785228;