1-74571998-C-T

Variant names:

• chr1-74571998-C-T
• NM_001002912.5:c.3712G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001002912.5(ERICH3):​c.3712G>A​(p.Gly1238Ser) 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. 15/21 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: 0.918
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088297784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERICH3	NM_001002912.5	c.3712G>A	p.Gly1238Ser	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.3712G>A	p.Gly1238Ser	missense_variant	Exon 14 of 15	5	NM_001002912.5	ENSP00000322609.5
ERICH3	ENST00000433746.2	n.1854G>A		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

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3712G>A (p.G1238S) alteration is located in exon 14 (coding exon 14) of the ERICH3 gene. This alteration results from a G to A substitution at nucleotide position 3712, causing the glycine (G) at amino acid position 1238 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.81
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.92
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.0080
Sift	Uncertain	0.016	D
Sift4G	Benign	0.28	T
Polyphen		0.015	B
Vest4		0.21
MutPred		0.30		Gain of phosphorylation at G1238 (P = 0.0427);
MVP		0.061
MPC		0.068
ClinPred		0.22	T
GERP RS		2.0
Varity_R		0.059
gMVP		0.034
Mutation Taster		=98/2	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

hg19: chr1-75037682;