chr1-74589767-A-C

Position:

• chr1-74589767-A-C

Variant summary

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

The NM_001002912.5(ERICH3):​c.2040T>G​(p.Ile680Met) 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. 14/20 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)
• Consequence: ERICH3 NM_001002912.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0320

Genes affected

ERICH3 (HGNC:25346): (glutamate rich 3)

ERICH3-AS1 (HGNC:41093): (ERICH3 antisense RNA 1)

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=0.04902476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERICH3	NM_001002912.5	c.2040T>G	p.Ile680Met	missense_variant	12/15	ENST00000326665.10	NP_001002912.4
ERICH3	XM_017000275.2	c.2034T>G	p.Ile678Met	missense_variant	12/14		XP_016855764.1
ERICH3-AS1	NR_121670.1	n.33A>C		non_coding_transcript_exon_variant	1/3
ERICH3-AS1	NR_121671.1	n.80+12258A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERICH3	ENST00000326665.10	c.2040T>G	p.Ile680Met	missense_variant	12/15	5	NM_001002912.5	ENSP00000322609.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.2040T>G (p.I680M) alteration is located in exon 12 (coding exon 12) of the ERICH3 gene. This alteration results from a T to G substitution at nucleotide position 2040, causing the isoleucine (I) at amino acid position 680 to be replaced by a methionine (M). 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	0.087
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.72
DEOGEN2	Benign	0.0099	T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L;.
PROVEAN	Benign	-0.11	N;N
REVEL	Benign	0.0070
Sift	Benign	0.31	T;T
Sift4G	Benign	0.086	T;T
Polyphen		0.45	P;B
Vest4		0.15
MutPred		0.21		Gain of phosphorylation at T677 (P = 0.1149);.;
MVP		0.040
MPC		0.13
ClinPred		0.077	T
GERP RS		0.47
Varity_R		0.058
gMVP		0.030

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: chr1-75055451;