NM_058187.5:c.868T>C

Variant names:

• chr21-32503934-T-C
• NM_058187.5:c.868T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_058187.5(EVA1C):​c.868T>C​(p.Phe290Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EVA1C NM_058187.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060802102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1C	NM_058187.5	c.868T>C	p.Phe290Leu	missense_variant	Exon 7 of 8	ENST00000300255.7	NP_478067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVA1C	ENST00000300255.7	c.868T>C	p.Phe290Leu	missense_variant	Exon 7 of 8	1	NM_058187.5	ENSP00000300255.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458226 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725474

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.5
DANN	Benign	0.78
DEOGEN2	Benign	0.013	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.061	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.090
MutPred		0.40		Loss of helix (P = 0.0821);.;.;
MVP		0.088
MPC		0.34
ClinPred		0.030	T
GERP RS		0.98
Varity_R		0.042
gMVP		0.57

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-33876244;