NM_058187.5:c.1054C>A

Variant names:

• chr21-32514918-C-A
• rs140738179
• NM_058187.5:c.1054C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_058187.5(EVA1C):​c.1054C>A​(p.Arg352Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R352H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EVA1C NM_058187.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.670
• Publications: 4 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]

TCP10L (HGNC:11657): (t-complex 10 like) Enables several functions, including identical protein binding activity; protein self-association; and transcription corepressor activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10063979).

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.1054C>A	p.Arg352Ser	missense	Exon 8 of 8	NP_478067.2
	EVA1C	NM_001286556.2		c.1045C>A	p.Arg349Ser	missense	Exon 8 of 8	NP_001273485.1	P58658-3
	EVA1C	NM_001320745.2		c.769C>A	p.Arg257Ser	missense	Exon 8 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.1054C>A	p.Arg352Ser	missense	Exon 8 of 8	ENSP00000300255.2	P58658-1
	EVA1C	ENST00000382699.7	TSL:1	c.1045C>A	p.Arg349Ser	missense	Exon 8 of 8	ENSP00000372146.3	P58658-3
	EVA1C	ENST00000437338.5	TSL:1	n.*644C>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000389291.1	A0A0C4DG64

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250928 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00000137 AC: 2 AN: 1461840 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.67
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.094
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.035	D
Polyphen		0.038	B
Vest4		0.14
MutPred		0.47		Loss of helix (P = 0.028)
MVP		0.26
MPC		0.35
ClinPred		0.070	T
GERP RS		2.6
Varity_R		0.16
gMVP		0.20
Mutation Taster		=96/4	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: rs140738179; hg19: chr21-33887228;