Genetic Variant ERMN:p.Thr243Ile (chr2-157321398-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020711.3(ERMN):c.728C>T(p.Thr243Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T243N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ERMN
NM_020711.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.602

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02392602).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020711.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERMN	NM_020711.3	MANE Select	c.728C>T	p.Thr243Ile	missense	Exon 3 of 3	NP_065762.1	Q8TAM6-1
ERMN	NM_001009959.3		c.767C>T	p.Thr256Ile	missense	Exon 4 of 4	NP_001009959.1	Q8TAM6-2
ERMN	NM_001304344.2		c.728C>T	p.Thr243Ile	missense	Exon 4 of 4	NP_001291273.1	Q8TAM6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERMN	ENST00000410096.6	TSL:1 MANE Select	c.728C>T	p.Thr243Ile	missense	Exon 3 of 3	ENSP00000387047.1	Q8TAM6-1
ERMN	ENST00000397283.6	TSL:2	c.767C>T	p.Thr256Ile	missense	Exon 4 of 4	ENSP00000380453.2	Q8TAM6-2
ERMN	ENST00000875547.1		c.728C>T	p.Thr243Ile	missense	Exon 4 of 4	ENSP00000545606.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249206

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111978

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.8

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.015

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.18

M_CAP

Benign

0.0020

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.60

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.5

REVEL

Benign

0.028

Sift

Benign

0.22

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.023

MutPred

0.14

Loss of phosphorylation at T243 (P = 0.0276)

MVP

0.072

MPC

0.036

ClinPred

0.059

GERP RS

-3.2

Varity_R

0.034

gMVP

0.13

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over