20-41361851-G-A

Position:

• chr20-41361851-G-A

Variant summary

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

The ENST00000332312.4(EMILIN3):​c.1718C>T​(p.Ala573Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EMILIN3 ENST00000332312.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83

Genes affected

EMILIN3 (HGNC:16123): (elastin microfibril interfacer 3) Enables identical protein binding activity. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

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=0.20096385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMILIN3	NM_052846.2	c.1718C>T	p.Ala573Val	missense_variant	4/4	ENST00000332312.4	NP_443078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMILIN3	ENST00000332312.4	c.1718C>T	p.Ala573Val	missense_variant	4/4	1	NM_052846.2	ENSP00000332806	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2024

The c.1718C>T (p.A573V) alteration is located in exon 4 (coding exon 4) of the EMILIN3 gene. This alteration results from a C to T substitution at nucleotide position 1718, causing the alanine (A) at amino acid position 573 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.20	T
MetaSVM	Uncertain	0.046	D
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.63	D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.26
Sift	Benign	1.0	T
Sift4G	Benign	0.43	T
Polyphen		0.96	P
Vest4		0.14
MutPred		0.21		Gain of catalytic residue at A573 (P = 0.0344);
MVP		0.86
MPC		0.20
ClinPred		0.90	D
GERP RS		3.8
Varity_R		0.095
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs949345254; hg19: chr20-39990491;