chr22-29206057-T-G

Variant names:

• chr22-29206057-T-G
• rs2039634933
• NM_133455.4:c.19T>G

Variant summary

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

The NM_001410828.1(EMID1):​c.19T>G​(p.Trp7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000244 in 1,228,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: EMID1 NM_001410828.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.107
• Publications: 0 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]

LOC101929638 (HGNC:):

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001410828.1. 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.19T>G	p.Trp7Gly	missense	Exon 1 of 15	NP_597712.2
	EMID1	NM_001410828.1		c.19T>G	p.Trp7Gly	missense	Exon 1 of 15	NP_001397757.1
	EMID1	NM_001267895.2		c.19T>G	p.Trp7Gly	missense	Exon 1 of 15	NP_001254824.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMID1	ENST00000334018.11	TSL:1 MANE Select	c.19T>G	p.Trp7Gly	missense	Exon 1 of 15	ENSP00000335481.6
	EMID1	ENST00000935682.1		c.19T>G	p.Trp7Gly	missense	Exon 1 of 16	ENSP00000605741.1
	EMID1	ENST00000961474.1		c.19T>G	p.Trp7Gly	missense	Exon 1 of 16	ENSP00000631533.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151792 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000186 AC: 2 AN: 1077200 Hom.: 0 Cov.: 30 AF XY: 0.00000197 AC XY: 1 AN XY: 508654

African (AFR) AF: 0.00 AC: 0 AN: 22804

American (AMR) AF: 0.00 AC: 0 AN: 8304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14248

East Asian (EAS) AF: 0.00 AC: 0 AN: 26430

South Asian (SAS) AF: 0.000103 AC: 2 AN: 19466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2910

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 918478

Other (OTH) AF: 0.00 AC: 0 AN: 43502

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151792 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74132

African (AFR) AF: 0.00 AC: 0 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67888

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.083	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.11
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.097	T
Polyphen		0.98	D
Vest4		0.46
MutPred		0.70		Gain of disorder (P = 0.003)
MVP		0.91
MPC		0.77
ClinPred		0.71	D
GERP RS		3.7
PromoterAI		-0.011	Neutral
gMVP		0.21
Mutation Taster		=87/13	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: rs2039634933; hg19: chr22-29602046;