chr8-98089661-C-T

Variant names:

• chr8-98089661-C-T
• rs769493833
• NM_173549.3:c.644C>T

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.644C>T​(p.Ala215Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,966 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. A215S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (1 hom.)
• Consequence: ERICH5 NM_173549.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.116
• 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=0.043516964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173549.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERICH5	NM_173549.3	MANE Select	c.644C>T	p.Ala215Val	missense	Exon 2 of 3	NP_775820.2	Q6P6B1-1
	ERICH5	NM_001170806.2		c.59-3560C>T		intron	N/A	NP_001164277.1	Q6P6B1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERICH5	ENST00000318528.8	TSL:1 MANE Select	c.644C>T	p.Ala215Val	missense	Exon 2 of 3	ENSP00000315614.3	Q6P6B1-1
	ERICH5	ENST00000890870.1		c.731C>T	p.Ala244Val	missense	Exon 3 of 4	ENSP00000560929.1
	ERICH5	ENST00000890869.1		c.653C>T	p.Ala218Val	missense	Exon 2 of 3	ENSP00000560928.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000321 AC: 8 AN: 249522 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000356

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461804 Hom.: 1 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727204

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000894 AC: 4 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

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

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111998

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152162 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74332

African (AFR) AF: 0.0000483 AC: 2 AN: 41430

American (AMR) AF: 0.000196 AC: 3 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.12
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.014
Sift	Benign	0.19	T
Sift4G	Benign	0.21	T
Polyphen		0.0040	B
Vest4		0.082
MutPred		0.13		Loss of loop (P = 0.1258)
MVP		0.061
MPC		0.065
ClinPred		0.042	T
GERP RS		-0.19
Varity_R		0.036
gMVP		0.027
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: rs769493833; hg19: chr8-99101889;