rs116599532

Variant names:

• chr2-157321563-T-C
• rs116599532
• NM_020711.3:c.563A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020711.3(ERMN):​c.563A>G​(p.Asp188Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,614,066 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: ERMN NM_020711.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0077876747).

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.563A>G	p.Asp188Gly	missense	Exon 3 of 3	NP_065762.1	Q8TAM6-1
	ERMN	NM_001009959.3		c.602A>G	p.Asp201Gly	missense	Exon 4 of 4	NP_001009959.1	Q8TAM6-2
	ERMN	NM_001304344.2		c.563A>G	p.Asp188Gly	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.563A>G	p.Asp188Gly	missense	Exon 3 of 3	ENSP00000387047.1	Q8TAM6-1
	ERMN	ENST00000397283.6	TSL:2	c.602A>G	p.Asp201Gly	missense	Exon 4 of 4	ENSP00000380453.2	Q8TAM6-2
	ERMN	ENST00000875547.1		c.563A>G	p.Asp188Gly	missense	Exon 4 of 4	ENSP00000545606.1

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00121

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000843 AC: 21 AN: 249230 AF XY: 0.0000518

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.0000290

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: 0.000165

GnomAD4 exome AF: 0.0000445 AC: 65 AN: 1461796 Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30 AN XY: 727194

African (AFR) AF: 0.00149 AC: 50 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111942

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74468

African (AFR) AF: 0.00120 AC: 50 AN: 41556

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000161 Hom.: 0

Bravo AF: 0.000465

ESP6500AA AF: 0.00156 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000132 AC: 16

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	0.091
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.073
Sift	Benign	0.080	T
Sift4G	Benign	0.38	T
Polyphen		0.0090	B
Vest4		0.10
MVP		0.12
MPC		0.080
ClinPred		0.024	T
GERP RS		4.9
Varity_R		0.12
gMVP		0.033
Mutation Taster		=83/17	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: rs116599532; hg19: chr2-158178075;