rs534023088

Variant names:

• chr2-27079166-G-A
• rs534023088
• NM_007046.4:c.101G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-27079166-G-A
• chr2-27079166-G-T

Variant summary

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

The NM_007046.4(EMILIN1):​c.101G>A​(p.Gly34Asp) variant causes a missense change involving the alteration of a non-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. G34V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EMILIN1 NM_007046.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 0 publications found

Genes affected

EMILIN1 (HGNC:19880): (elastin microfibril interfacer 1) This gene encodes an extracellular matrix glycoprotein that is characterized by an N-terminal microfibril interface domain, a coiled-coiled alpha-helical domain, a collagenous domain and a C-terminal globular C1q domain. The encoded protein associates with elastic fibers at the interface between elastin and microfibrils and may play a role in the development of elastic tissues including large blood vessels, dermis, heart and lung. [provided by RefSeq, Sep 2009]

EMILIN1 Gene-Disease associations (from GenCC):

• neuronopathy, distal hereditary motor, autosomal dominant 10

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMILIN1	NM_007046.4	c.101G>A	p.Gly34Asp	missense_variant	Exon 1 of 8	ENST00000380320.9	NP_008977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMILIN1	ENST00000380320.9	c.101G>A	p.Gly34Asp	missense_variant	Exon 1 of 8	1	NM_007046.4	ENSP00000369677.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 212476 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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 Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.34
Sift	Benign	0.054	T
Sift4G	Benign	0.15	T
Polyphen		0.70	P
Vest4		0.73
MutPred		0.14		Loss of catalytic residue at S36 (P = 0.0387);
MVP		0.76
MPC		0.73
ClinPred		0.31	T
GERP RS		1.7
Varity_R		0.076
gMVP		0.71
Mutation Taster		=90/10	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: rs534023088; hg19: chr2-27302034;