2-157321398-G-C

Variant names:

• chr2-157321398-G-C
• rs767158796
• NM_020711.3:c.728C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020711.3(ERMN):​c.728C>G​(p.Thr243Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ERMN NM_020711.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602
• Publications: 0 publications found

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]

ACMG classification

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=0.017829597).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMN	NM_020711.3	MANE Select	c.728C>G	p.Thr243Ser	missense	Exon 3 of 3	NP_065762.1	Q8TAM6-1
	ERMN	NM_001009959.3		c.767C>G	p.Thr256Ser	missense	Exon 4 of 4	NP_001009959.1	Q8TAM6-2
	ERMN	NM_001304344.2		c.728C>G	p.Thr243Ser	missense	Exon 4 of 4	NP_001291273.1	Q8TAM6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMN	ENST00000410096.6	TSL:1 MANE Select	c.728C>G	p.Thr243Ser	missense	Exon 3 of 3	ENSP00000387047.1	Q8TAM6-1
	ERMN	ENST00000397283.6	TSL:2	c.767C>G	p.Thr256Ser	missense	Exon 4 of 4	ENSP00000380453.2	Q8TAM6-2
	ERMN	ENST00000875547.1		c.728C>G	p.Thr243Ser	missense	Exon 4 of 4	ENSP00000545606.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.78
DANN	Benign	0.18
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.60
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.036
Sift	Benign	0.91	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.023
MutPred		0.10		Gain of phosphorylation at S248 (P = 0.1132)
MVP		0.048
MPC		0.032
ClinPred		0.013	T
GERP RS		-3.2
Varity_R		0.028
gMVP		0.067
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs767158796; hg19: chr2-158177910;