8-98089597-G-T

Variant names:

• chr8-98089597-G-T
• rs753156887
• NM_173549.3:c.580G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173549.3(ERICH5):​c.580G>T​(p.Val194Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V194I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: ERICH5 NM_173549.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09237307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERICH5	NM_173549.3	c.580G>T	p.Val194Phe	missense_variant	Exon 2 of 3	ENST00000318528.8	NP_775820.2
ERICH5	NM_001170806.2	c.59-3624G>T		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.580G>T	p.Val194Phe	missense_variant	Exon 2 of 3	1	NM_173549.3	ENSP00000315614.3
ERICH5	ENST00000545282.1	c.59-3624G>T		intron_variant	Intron 1 of 1	2		ENSP00000440297.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250754 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461856 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.49
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.056
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.048
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.098	T
Polyphen		0.39	B
Vest4		0.16
MutPred		0.20		Gain of catalytic residue at V194 (P = 0.1128);
MVP		0.10
MPC		0.066
ClinPred		0.087	T
GERP RS		-1.4
Varity_R		0.12
gMVP		0.062
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

dbSNP: rs753156887; hg19: chr8-99101825;