Genetic Variant EMID1:p.Pro4Ser (chr22-29206048-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

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

The NM_133455.4(EMID1):c.10C>T(p.Pro4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,227,536 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 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

EMID1
NM_133455.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.274

Variant links:

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]

EMID1 links:

LOC101929638 (HGNC:):

LOC101929638 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.3538853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMID1	NM_133455.4 link	c.10C>T	p.Pro4Ser	missense_variant	Exon 1 of 15	ENST00000334018.11	NP_597712.2	Q96A84-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMID1	ENST00000334018.11 link	c.10C>T	p.Pro4Ser	missense_variant	Exon 1 of 15	1	NM_133455.4	ENSP00000335481.6		Q96A84-3

Frequencies

GnomAD3 genomes

AF:

0.000198

AC:

AN:

151802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

AC:

AN:

228

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1075734

Hom.:

Cov.:

AF XY:

0.00000591

AC XY:

AN XY:

507920

show subpopulations

Gnomad4 AFR exome

AF:

0.000528

AC:

AN:

22730

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

8230

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

14186

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

26344

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

19456

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

21010

Gnomad4 NFE exome

AF:

0.00

AC:

AN:

917500

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

43370

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000198

AC:

AN:

151802

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.000676

AC:

0.000676002

AN:

0.000676002

Gnomad4 AMR

AF:

0.000131

AC:

0.000131148

AN:

0.000131148

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000193

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 09, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.10C>T (p.P4S) alteration is located in exon 1 (coding exon 1) of the EMID1 gene. This alteration results from a C to T substitution at nucleotide position 10, causing the proline (P) at amino acid position 4 to be replaced by a serine (S). 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

-0.19

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

.;T;T;T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.099

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.83

T;T;T;T;T

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.35

T;T;T;T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

0.81

L;.;.;.;.

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.0

N;N;N;N;N

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Benign

0.12

T;T;T;T;T

Polyphen

1.0

D;.;D;P;.

Vest4

0.20

MVP

0.94

MPC

0.16

ClinPred

0.61

GERP RS

2.4

gMVP

0.16

Mutation Taster

=91/9

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over