8-98089322-A-G

Variant names:

• chr8-98089322-A-G
• NM_173549.3:c.305A>G

Variant summary

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

The NM_173549.3(ERICH5):​c.305A>G​(p.Glu102Gly) 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. 14/21 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. E102K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ERICH5 NM_173549.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.759
• Publications: 0 publications found

Genes affected

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

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=0.061279476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERICH5	NM_173549.3	c.305A>G	p.Glu102Gly	missense_variant	Exon 2 of 3	ENST00000318528.8	NP_775820.2
ERICH5	NM_001170806.2	c.59-3899A>G		intron_variant	Intron 1 of 1		NP_001164277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERICH5	ENST00000318528.8	c.305A>G	p.Glu102Gly	missense_variant	Exon 2 of 3	1	NM_173549.3	ENSP00000315614.3
ERICH5	ENST00000545282.1	c.59-3899A>G		intron_variant	Intron 1 of 1	2		ENSP00000440297.1

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

Mar 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.305A>G (p.E102G) alteration is located in exon 2 (coding exon 2) of the ERICH5 gene. This alteration results from a A to G substitution at nucleotide position 305, causing the glutamic acid (E) at amino acid position 102 to be replaced by a glycine (G). 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	0.094
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.76
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.085
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.027	D
Polyphen		0.033	B
Vest4		0.11
MutPred		0.094		Gain of glycosylation at T104 (P = 0.0856);
MVP		0.23
MPC		0.30
ClinPred		0.72	D
GERP RS		3.7
Varity_R		0.15
gMVP		0.053
Mutation Taster		=99/1	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

hg19: chr8-99101550;