2-157321383-C-T

Variant names:

• chr2-157321383-C-T
• NM_020711.3:c.743G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020711.3(ERMN):​c.743G>A​(p.Ser248Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ERMN NM_020711.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.429

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

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=0.014885187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERMN	NM_020711.3	c.743G>A	p.Ser248Asn	missense_variant	Exon 3 of 3	ENST00000410096.6	NP_065762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERMN	ENST00000410096.6	c.743G>A	p.Ser248Asn	missense_variant	Exon 3 of 3	1	NM_020711.3	ENSP00000387047.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.782G>A (p.S261N) alteration is located in exon 4 (coding exon 4) of the ERMN gene. This alteration results from a G to A substitution at nucleotide position 782, causing the serine (S) at amino acid position 261 to be replaced by an asparagine (N). 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	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.2
DANN	Benign	0.21
DEOGEN2	Benign	0.0034	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.015	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.11	N;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.72	N;N;N
REVEL	Benign	0.061
Sift	Benign	0.97	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.048
MutPred		0.10		Loss of phosphorylation at S248 (P = 0.0453);.;.;
MVP		0.067
MPC		0.033
ClinPred		0.039	T
GERP RS		0.39
Varity_R		0.044
gMVP		0.021

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-158177895;