22-29225172-G-A

Position:

• chr22-29225172-G-A

Variant summary

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

The NM_133455.4(EMID1):​c.359G>A​(p.Gly120Asp) 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. 12/18 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: 33)
• Consequence: EMID1 NM_133455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.796

Genes affected

EMID1 (HGNC:18036): (EMI domain containing 1) Predicted to be located in several cellular components, including Golgi apparatus; endoplasmic reticulum; and extracellular matrix. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

EMID1 (HGNC:):

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=0.14118907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMID1	NM_133455.4	c.359G>A	p.Gly120Asp	missense_variant	4/15	ENST00000334018.11	NP_597712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMID1	ENST00000334018.11	c.359G>A	p.Gly120Asp	missense_variant	4/15	1	NM_133455.4	ENSP00000335481.6

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

Sep 08, 2024

The c.359G>A (p.G120D) alteration is located in exon 4 (coding exon 4) of the EMID1 gene. This alteration results from a G to A substitution at nucleotide position 359, causing the glycine (G) at amino acid position 120 to be replaced by an aspartic acid (D). 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
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.029	.;T;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Uncertain	-0.13	T
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.37	T;T;T;T
Polyphen		0.12	B;.;B;D
Vest4		0.39
MutPred		0.35		Loss of catalytic residue at G120 (P = 0.0318);Loss of catalytic residue at G120 (P = 0.0318);Loss of catalytic residue at G120 (P = 0.0318);Loss of catalytic residue at G120 (P = 0.0318);
MVP		0.83
MPC		0.16
ClinPred		0.46	T
GERP RS		3.6
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1039978717; hg19: chr22-29621161;