8-673294-T-C

Variant summary

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

The NM_207332.3(ERICH1):c.1058A>G(p.Tyr353Cys) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ERICH1 NM_207332.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.535

Genes affected

ERICH1 (HGNC:27234): (glutamate rich 1)

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=0.25405616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERICH1	NM_207332.3	c.1058A>G	p.Tyr353Cys	missense_variant	4/6	ENST00000262109.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERICH1	ENST00000262109.8	c.1058A>G	p.Tyr353Cys	missense_variant	4/6	1	NM_207332.3	P2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

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

Jun 06, 2022

The c.1058A>G (p.Y353C) alteration is located in exon 4 (coding exon 4) of the ERICH1 gene. This alteration results from a A to G substitution at nucleotide position 1058, causing the tyrosine (Y) at amino acid position 353 to be replaced by a cysteine (C). 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	0.24
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.84	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.067
Sift	Benign	0.089	T;T
Sift4G	Benign	0.078	T;T
Polyphen		0.54	P;D
Vest4		0.22
MutPred		0.39		.;Loss of phosphorylation at Y353 (P = 0.0242);
MVP		0.51
MPC		0.040
ClinPred		0.92	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.031

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr8-623294;