Genetic Variant ERMN:p.Ser123Ile (chr2-157321758-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020711.3(ERMN):c.368G>T(p.Ser123Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,612,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ERMN
NM_020711.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.258

Variant links:

Genes affected

ERMN (HGNC:29208): (ermin) Predicted to enable actin filament binding activity. Involved in actin filament organization; regulation of cell projection organization; and regulation of cell shape. Located in cell cortex; internode region of axon; and paranode region of axon. [provided by Alliance of Genome Resources, Apr 2022]

ERMN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062166035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERMN	NM_020711.3 link	c.368G>T	p.Ser123Ile	missense_variant	Exon 3 of 3	ENST00000410096.6	NP_065762.1	Q8TAM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERMN	ENST00000410096.6 link	c.368G>T	p.Ser123Ile	missense_variant	Exon 3 of 3	1	NM_020711.3	ENSP00000387047.1		Q8TAM6-1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000283

AC:

AN:

247710

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134484

show subpopulations

Gnomad AFR exome

AF:

0.000452

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000548

AC:

AN:

1459902

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726236

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

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

AF:

0.0000985

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000762

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000264

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 31, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.407G>T (p.S136I) alteration is located in exon 4 (coding exon 4) of the ERMN gene. This alteration results from a G to T substitution at nucleotide position 407, causing the serine (S) at amino acid position 136 to be replaced by an isoleucine (I). 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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

T;.;.;T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.68

T;T;T;T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.062

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.8

D;D;D;D;D

REVEL

Benign

0.096

Sift

Uncertain

0.0050

D;D;D;D;D

Sift4G

Benign

0.15

T;T;T;.;.

Polyphen

0.96

D;D;D;.;.

Vest4

0.19

MVP

0.29

MPC

0.24

ClinPred

0.36

GERP RS

1.1

Varity_R

0.15

gMVP

0.23

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