22-29214982-C-A

Variant names:

• chr22-29214982-C-A
• rs767276600
• NM_133455.4:c.158C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_133455.4(EMID1):​c.158C>A​(p.Thr53Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000444 in 1,553,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: EMID1 NM_133455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40952152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMID1	NM_133455.4	c.158C>A	p.Thr53Asn	missense_variant	Exon 2 of 15	ENST00000334018.11	NP_597712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMID1	ENST00000334018.11	c.158C>A	p.Thr53Asn	missense_variant	Exon 2 of 15	1	NM_133455.4	ENSP00000335481.6

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000231 AC: 38 AN: 164716 AF XY: 0.000138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000153

Gnomad OTH exome AF: 0.000657

GnomAD4 exome AF: 0.0000457 AC: 64 AN: 1401560 Hom.: 0 Cov.: 31 AF XY: 0.0000390 AC XY: 27 AN XY: 691592

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 32018

Gnomad4 AMR exome AF: 0.00122 AC: 44 AN: 36156

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25160

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 36360

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 79162

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 49524

Gnomad4 NFE exome AF: 0.00000926 AC: 10 AN: 1079402

Gnomad4 Remaining exome AF: 0.0000516 AC: 3 AN: 58092

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74372

Gnomad4 AFR AF: 0.0000241 AC: 0.0000241185 AN: 0.0000241185

Gnomad4 AMR AF: 0.000262 AC: 0.000261712 AN: 0.000261712

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00 AC: 0 AN: 0

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000805 AC: 9

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.158C>A (p.T53N) alteration is located in exon 2 (coding exon 2) of the EMID1 gene. This alteration results from a C to A substitution at nucleotide position 158, causing the threonine (T) at amino acid position 53 to be replaced by an asparagine (N). 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	-0.31	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;T;T;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.41	T;T;T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Pathogenic	3.0	M;.;.;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.4	N;D;D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;.;D;D;.
Vest4		0.76
MutPred		0.68		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.79
MPC		0.61
ClinPred		0.20	T
GERP RS		5.2
gMVP		0.50
Mutation Taster		=62/38	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

Publications

LitVar

Other links and lift over

dbSNP: rs767276600; hg19: chr22-29610971;