rs775296669

Variant names:

• chr2-157321696-C-A
• rs775296669
• NM_020711.3:c.430G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020711.3(ERMN):​c.430G>T​(p.Asp144Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ERMN NM_020711.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.408
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.085950166).

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.430G>T	p.Asp144Tyr	missense	Exon 3 of 3	NP_065762.1	Q8TAM6-1
	ERMN	NM_001009959.3		c.469G>T	p.Asp157Tyr	missense	Exon 4 of 4	NP_001009959.1	Q8TAM6-2
	ERMN	NM_001304344.2		c.430G>T	p.Asp144Tyr	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.430G>T	p.Asp144Tyr	missense	Exon 3 of 3	ENSP00000387047.1	Q8TAM6-1
	ERMN	ENST00000397283.6	TSL:2	c.469G>T	p.Asp157Tyr	missense	Exon 4 of 4	ENSP00000380453.2	Q8TAM6-2
	ERMN	ENST00000875547.1		c.430G>T	p.Asp144Tyr	missense	Exon 4 of 4	ENSP00000545606.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249300 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR 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: 0.0000157 AC: 23 AN: 1461772 Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18 AN XY: 727188

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111950

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.41
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.088
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.23
MutPred		0.18		Gain of phosphorylation at D144 (P = 0.0086)
MVP		0.18
MPC		0.24
ClinPred		0.57	D
GERP RS		4.0
Varity_R		0.22
gMVP		0.15
Mutation Taster		=89/11	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: rs775296669; hg19: chr2-158178208;