8-98089321-G-A

Variant names:

• chr8-98089321-G-A
• NM_173549.3:c.304G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173549.3(ERICH5):​c.304G>A​(p.Glu102Lys) 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. 12/20 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. E102G) 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: 1.21

Genes affected

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

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=0.054002345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERICH5	NM_173549.3	c.304G>A	p.Glu102Lys	missense_variant	Exon 2 of 3	ENST00000318528.8	NP_775820.2
ERICH5	NM_001170806.2	c.59-3900G>A		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.304G>A	p.Glu102Lys	missense_variant	Exon 2 of 3	1	NM_173549.3	ENSP00000315614.3
ERICH5	ENST00000545282.1	c.59-3900G>A		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.304G>A (p.E102K) alteration is located in exon 2 (coding exon 2) of the ERICH5 gene. This alteration results from a G to A substitution at nucleotide position 304, causing the glutamic acid (E) at amino acid position 102 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	0.097
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.023
Sift	Benign	0.29	T
Sift4G	Benign	0.17	T
Polyphen		0.13	B
Vest4		0.17
MutPred		0.22		Gain of methylation at E102 (P = 0.0075);
MVP		0.12
MPC		0.27
ClinPred		0.60	D
GERP RS		3.0
Varity_R		0.13
gMVP		0.083

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: chr8-99101549; COSMIC: COSV59315286;