21-32457651-C-A

Variant names:

• chr21-32457651-C-A
• rs200043057
• NM_058187.5:c.412C>A

Variant summary

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

The NM_058187.5(EVA1C):​c.412C>A​(p.Arg138Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R138H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EVA1C NM_058187.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.36
• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058187.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVA1C	NM_058187.5	MANE Select	c.412C>A	p.Arg138Ser	missense	Exon 3 of 8	NP_478067.2
	EVA1C	NM_001286556.2		c.412C>A	p.Arg138Ser	missense	Exon 3 of 8	NP_001273485.1	P58658-3
	EVA1C	NM_001320745.2		c.127C>A	p.Arg43Ser	missense	Exon 3 of 8	NP_001307674.1	B3KWG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVA1C	ENST00000300255.7	TSL:1 MANE Select	c.412C>A	p.Arg138Ser	missense	Exon 3 of 8	ENSP00000300255.2	P58658-1
	EVA1C	ENST00000382699.7	TSL:1	c.412C>A	p.Arg138Ser	missense	Exon 3 of 8	ENSP00000372146.3	P58658-3
	EVA1C	ENST00000437338.5	TSL:1	n.*2C>A		non_coding_transcript_exon	Exon 2 of 7	ENSP00000389291.1	A0A0C4DG64

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L
PhyloP100		7.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.29
Sift	Benign	0.087	T
Sift4G	Benign	0.12	T
Polyphen		0.97	D
Vest4		0.67
MutPred		0.50		Gain of glycosylation at R138 (P = 0.0332)
MVP		0.25
MPC		1.1
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.56
gMVP		0.54
Mutation Taster		=59/41	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

dbSNP: rs200043057; hg19: chr21-33829959;