22-29225139-C-T

Variant names:

• chr22-29225139-C-T
• rs743920
• NM_133455.4:c.326C>T

Variant summary

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

The NM_133455.4(EMID1):​c.326C>T​(p.Ala109Val) 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. 11/18 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: 34)
• Consequence: EMID1 NM_133455.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

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]

LOC105372985 (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=0.08761138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMID1	NM_133455.4	c.326C>T	p.Ala109Val	missense_variant	Exon 4 of 15	ENST00000334018.11	NP_597712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMID1	ENST00000334018.11	c.326C>T	p.Ala109Val	missense_variant	Exon 4 of 15	1	NM_133455.4	ENSP00000335481.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	.;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.40	T;T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.088	T;T;T;T
MetaSVM	Benign	-0.59	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.032	D;T;T;D
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.087	B;.;B;B
Vest4		0.24
MutPred		0.26		Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);
MVP		0.56
MPC		0.13
ClinPred		0.14	T
GERP RS		1.3
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs743920; hg19: chr22-29621128;