NM_133455.4:c.326C>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/20 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
• Publications: 23 publications found

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

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=0.08761138).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133455.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMID1	NM_133455.4	MANE Select	c.326C>T	p.Ala109Val	missense	Exon 4 of 15	NP_597712.2	Q96A84-3
	EMID1	NM_001410828.1		c.326C>T	p.Ala109Val	missense	Exon 4 of 15	NP_001397757.1	B0QYK5
	EMID1	NM_001267895.2		c.320C>T	p.Ala107Val	missense splice_region	Exon 4 of 15	NP_001254824.1	Q96A84-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMID1	ENST00000334018.11	TSL:1 MANE Select	c.326C>T	p.Ala109Val	missense	Exon 4 of 15	ENSP00000335481.6	Q96A84-3
	EMID1	ENST00000935682.1		c.326C>T	p.Ala109Val	missense	Exon 4 of 16	ENSP00000605741.1
	EMID1	ENST00000961474.1		c.326C>T	p.Ala109Val	missense	Exon 4 of 16	ENSP00000631533.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 641

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.59	T
PhyloP100		0.44
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.11
Sift	Benign	0.032	D
Sift4G	Benign	0.11	T
Polyphen		0.087	B
Vest4		0.24
MutPred		0.26		Gain of sheet (P = 0.0125)
MVP		0.56
MPC		0.13
ClinPred		0.14	T
GERP RS		1.3
gMVP		0.26
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs743920; hg19: chr22-29621128;