1-74599710-C-T

Position:

• chr1-74599710-C-T

Variant summary

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

The NM_001002912.5(ERICH3):​c.1711G>A​(p.Glu571Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.15

Genes affected

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

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERICH3	NM_001002912.5	c.1711G>A	p.Glu571Lys	missense_variant	11/15	ENST00000326665.10	NP_001002912.4
ERICH3	XM_017000275.2	c.1705G>A	p.Glu569Lys	missense_variant	11/14		XP_016855764.1
ERICH3-AS1	NR_121670.1	n.173+9803C>T		intron_variant
ERICH3-AS1	NR_121671.1	n.81-15496C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERICH3	ENST00000326665.10	c.1711G>A	p.Glu571Lys	missense_variant	11/15	5	NM_001002912.5	ENSP00000322609.5
ERICH3	ENST00000420661.6	c.1120G>A	p.Glu374Lys	missense_variant	6/7	1		ENSP00000398581.2
ERICH3-AS1	ENST00000612390.4	n.81-15496C>T		intron_variant		1
ERICH3-AS1	ENST00000416017.1	n.173+9803C>T		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

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

Feb 07, 2023

The c.1711G>A (p.E571K) alteration is located in exon 11 (coding exon 11) of the ERICH3 gene. This alteration results from a G to A substitution at nucleotide position 1711, causing the glutamic acid (E) at amino acid position 571 to be replaced by a lysine (K). 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	0.18
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.21	T;T
Polyphen		1.0	D;D
Vest4		0.55
MutPred		0.14		Gain of ubiquitination at E571 (P = 0.0082);.;
MVP		0.13
MPC		0.15
ClinPred		0.83	D
GERP RS		5.1
Varity_R		0.23
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs759050964; hg19: chr1-75065394;