8-98089660-G-C

Variant names:

• chr8-98089660-G-C
• rs1031042023
• NM_173549.3:c.643G>C

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.643G>C​(p.Ala215Pro) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A215G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ERICH5 NM_173549.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 1 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=0.0387035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERICH5	NM_173549.3	c.643G>C	p.Ala215Pro	missense_variant	Exon 2 of 3	ENST00000318528.8	NP_775820.2
ERICH5	NM_001170806.2	c.59-3561G>C		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.643G>C	p.Ala215Pro	missense_variant	Exon 2 of 3	1	NM_173549.3	ENSP00000315614.3
ERICH5	ENST00000545282.1	c.59-3561G>C		intron_variant	Intron 1 of 1	2		ENSP00000440297.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.34
DANN	Benign	0.94
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00090	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.9
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.049
Sift	Benign	0.41	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.062
MutPred		0.20		Gain of catalytic residue at A215 (P = 0.0055);
MVP		0.048
MPC		0.12
ClinPred		0.091	T
GERP RS		-11
Varity_R		0.046
gMVP		0.017
Mutation Taster		=100/0	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

dbSNP: rs1031042023; hg19: chr8-99101888;