rs696698

chr1-74599757-C-Achr1-74599757-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 14/20 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

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=0.04502994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERICH3	NM_001002912.5	c.1664G>T	p.Arg555Leu	missense_variant	11/15	ENST00000326665.10
ERICH3-AS1	NR_121671.1	n.81-15449C>A		intron_variant, non_coding_transcript_variant
ERICH3	XM_017000275.2	c.1658G>T	p.Arg553Leu	missense_variant	11/14
ERICH3-AS1	NR_121670.1	n.173+9850C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERICH3	ENST00000326665.10	c.1664G>T	p.Arg555Leu	missense_variant	11/15	5	NM_001002912.5	P3
ERICH3	ENST00000420661.6	c.1073G>T	p.Arg358Leu	missense_variant	6/7	1		A2
ERICH3-AS1	ENST00000612390.4	n.81-15449C>A		intron_variant, non_coding_transcript_variant		1
ERICH3-AS1	ENST00000416017.1	n.173+9850C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	1.0	P;P
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.033
Sift	Benign	0.037	D;T
Sift4G	Benign	0.28	T;T
Polyphen		0.021	B;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

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

LitVar

Other links and lift over

dbSNP: rs696698; hg19: chr1-75065441;