1-74599757-C-A

Variant names:

• chr1-74599757-C-A
• rs696698
• NM_001002912.5:c.1664G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001002912.5(ERICH3):​c.1664G>T​(p.Arg555Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R555C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERICH3 NM_001002912.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 15 publications found

Genes affected

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04502994).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002912.5. 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
	ERICH3	NM_001002912.5	MANE Select	c.1664G>T	p.Arg555Leu	missense	Exon 11 of 15	NP_001002912.4
	ERICH3-AS1	NR_121670.1		n.173+9850C>A		intron	N/A
	ERICH3-AS1	NR_121671.1		n.81-15449C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERICH3	ENST00000326665.10	TSL:5 MANE Select	c.1664G>T	p.Arg555Leu	missense	Exon 11 of 15	ENSP00000322609.5	Q5RHP9-1
	ERICH3	ENST00000420661.6	TSL:1	c.1073G>T	p.Arg358Leu	missense	Exon 6 of 7	ENSP00000398581.2	Q5RHP9-3
	ERICH3-AS1	ENST00000612390.4	TSL:1	n.81-15449C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 912

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.4
DANN	Benign	0.41
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.048
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.033
Sift	Benign	0.037	D
Sift4G	Benign	0.28	T
Polyphen		0.021	B
Vest4		0.17
MutPred		0.14		Gain of helix (P = 0.0854)
MVP		0.048
MPC		0.019
ClinPred		0.066	T
GERP RS		-1.3
Varity_R		0.059
gMVP		0.025
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

dbSNP: rs696698; hg19: chr1-75065441;