22-29206120-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.82G>A(p.Ala28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000927 in 1,078,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: EMID1 NM_133455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.427

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]

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=0.23862633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMID1	NM_133455.4	c.82G>A	p.Ala28Thr	missense_variant	1/15	ENST00000334018.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMID1	ENST00000334018.11	c.82G>A	p.Ala28Thr	missense_variant	1/15	1	NM_133455.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.27e-7 AC: 1 AN: 1078438 Hom.: 0 Cov.: 30 AF XY: 0.00000196 AC XY: 1 AN XY: 509162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Mar 27, 2023

The c.82G>A (p.A28T) alteration is located in exon 1 (coding exon 1) of the EMID1 gene. This alteration results from a G to A substitution at nucleotide position 82, causing the alanine (A) at amino acid position 28 to be replaced by a threonine (T). 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	-0.088	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	16
Dann	Uncertain	0.99
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.82	T;T;T;T;T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.90	L;.;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.65	N;N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.27	T;T;T;T;T
Sift4G	Benign	0.59	T;T;T;T;T
Polyphen		0.29	B;.;B;B;.
Vest4		0.095
MutPred		0.30		Gain of glycosylation at A28 (P = 0.0932);Gain of glycosylation at A28 (P = 0.0932);Gain of glycosylation at A28 (P = 0.0932);Gain of glycosylation at A28 (P = 0.0932);Gain of glycosylation at A28 (P = 0.0932);
MVP		0.86
MPC		0.12
ClinPred		0.16	T
GERP RS		0.95
gMVP		0.14

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-29602109; COSMIC: COSV61828800;