4-5810428-G-T

Variant names:

• chr4-5810428-G-T
• rs35287723
• NM_153717.3:c.2872G>T

Variant summary

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

The NM_153717.3(EVC):​c.2872G>T​(p.Asp958Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D958N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EVC NM_153717.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

Genes affected

EVC (HGNC:3497): (EvC ciliary complex subunit 1) This gene encodes a protein containing a leucine zipper and a transmembrane domain. This gene has been implicated in both Ellis-van Creveld syndrome (EvC) and Weyers acrodental dysostosis. [provided by RefSeq, Jul 2008]

CRMP1 (HGNC:2365): (collapsin response mediator protein 1) This gene encodes a member of a family of cytosolic phosphoproteins expressed exclusively in the nervous system. The encoded protein is thought to be a part of the semaphorin signal transduction pathway implicated in semaphorin-induced growth cone collapse during neural development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

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=0.15303078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3	c.2872G>T	p.Asp958Tyr	missense_variant	Exon 20 of 21	ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11	c.2872G>T	p.Asp958Tyr	missense_variant	Exon 20 of 21	1	NM_153717.3	ENSP00000264956.6
CRMP1	ENST00000506216.5	n.1647+15066C>A		intron_variant	Intron 12 of 12	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Ellis-van Creveld syndrome Uncertain:1

Apr 15, 2025

Natera, Inc.

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Benign	0.88	T
Sift4G	Benign	0.12	T
Vest4		0.18
ClinPred		0.55	D
GERP RS		4.3
Varity_R		0.11
gMVP		0.21
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs35287723; hg19: chr4-5812155;