8-98089763-T-C

Position:

• chr8-98089763-T-C

Variant summary

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

The ENST00000318528.8(ERICH5):​c.746T>C​(p.Leu249Ser) 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 (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ERICH5 ENST00000318528.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.620

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=0.047679454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERICH5	NM_173549.3	c.746T>C	p.Leu249Ser	missense_variant	2/3	ENST00000318528.8	NP_775820.2
ERICH5	NM_001170806.2	c.59-3458T>C		intron_variant			NP_001164277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERICH5	ENST00000318528.8	c.746T>C	p.Leu249Ser	missense_variant	2/3	1	NM_173549.3	ENSP00000315614	P1
ERICH5	ENST00000545282.1	c.59-3458T>C		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 02, 2023

The c.746T>C (p.L249S) alteration is located in exon 2 (coding exon 2) of the ERICH5 gene. This alteration results from a T to C substitution at nucleotide position 746, causing the leucine (L) at amino acid position 249 to be replaced by a serine (S). 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	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.050
Sift	Benign	0.36	T
Sift4G	Benign	0.73	T
Polyphen		0.24	B
Vest4		0.084
MutPred		0.15		Gain of glycosylation at L249 (P = 0.0181);
MVP		0.13
MPC		0.094
ClinPred		0.13	T
GERP RS		-2.7
Varity_R		0.033
gMVP		0.089

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: chr8-99101991;