8-98089670-T-A

Position:

• chr8-98089670-T-A

Variant summary

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

The ENST00000318528.8(ERICH5):​c.653T>A​(p.Leu218Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L218P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ERICH5 ENST00000318528.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.03

Genes affected

ERICH5 (HGNC:26823): (glutamate rich 5)

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=0.108216494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERICH5	NM_173549.3	c.653T>A	p.Leu218Gln	missense_variant	2/3	ENST00000318528.8	NP_775820.2
ERICH5	NM_001170806.2	c.59-3551T>A		intron_variant			NP_001164277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERICH5	ENST00000318528.8	c.653T>A	p.Leu218Gln	missense_variant	2/3	1	NM_173549.3	ENSP00000315614	P1
ERICH5	ENST00000545282.1	c.59-3551T>A		intron_variant		2		ENSP00000440297

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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 14, 2022

The c.653T>A (p.L218Q) alteration is located in exon 2 (coding exon 2) of the ERICH5 gene. This alteration results from a T to A substitution at nucleotide position 653, causing the leucine (L) at amino acid position 218 to be replaced by a glutamine (Q). 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	0.096
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.2
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.027
Sift	Benign	0.14	T
Sift4G	Benign	0.061	T
Polyphen		0.72	P
Vest4		0.15
MutPred		0.21		Gain of glycosylation at S222 (P = 0.1093);
MVP		0.18
MPC		0.32
ClinPred		0.40	T
GERP RS		-4.3
Varity_R		0.13
gMVP		0.062

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-99101898;