1-74571155-C-G

Variant names:

• chr1-74571155-C-G
• NM_001002912.5:c.4555G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001002912.5(ERICH3):​c.4555G>C​(p.Glu1519Gln) 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. 13/20 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: 0.657

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16289404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERICH3	NM_001002912.5	c.4555G>C	p.Glu1519Gln	missense_variant	Exon 14 of 15	ENST00000326665.10	NP_001002912.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERICH3	ENST00000326665.10	c.4555G>C	p.Glu1519Gln	missense_variant	Exon 14 of 15	5	NM_001002912.5	ENSP00000322609.5
ERICH3	ENST00000433746.2	n.2697G>C		non_coding_transcript_exon_variant	Exon 2 of 3	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 87

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4555G>C (p.E1519Q) alteration is located in exon 14 (coding exon 14) of the ERICH3 gene. This alteration results from a G to C substitution at nucleotide position 4555, causing the glutamic acid (E) at amino acid position 1519 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.085
Sift	Uncertain	0.013	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.25
MutPred		0.16		Gain of sheet (P = 0.1208);
MVP		0.13
MPC		0.10
ClinPred		0.61	D
GERP RS		4.2
Varity_R		0.061
gMVP		0.077

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: chr1-75036839;