Genetic Variant HERPUD2:p.Arg355Leu (chr7-35633847-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022373.5(HERPUD2):c.1064G>T(p.Arg355Leu) 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. 13/22 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. R355H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HERPUD2
NM_022373.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.27

Publications

1 publications found

Variant links:

Genes affected

HERPUD2 (HGNC:21915): (HERPUD family member 2) Predicted to be involved in endoplasmic reticulum unfolded protein response. Predicted to act upstream of or within spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

HERPUD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.24409878).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022373.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HERPUD2	NM_022373.5	MANE Select	c.1064G>T	p.Arg355Leu	missense	Exon 9 of 9	NP_071768.3
HERPUD2	NM_001438072.1		c.1064G>T	p.Arg355Leu	missense	Exon 8 of 8	NP_001425001.1
HERPUD2	NM_001438070.1		c.872G>T	p.Arg291Leu	missense	Exon 7 of 7	NP_001424999.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HERPUD2	ENST00000311350.8	TSL:1 MANE Select	c.1064G>T	p.Arg355Leu	missense	Exon 9 of 9	ENSP00000310729.3	Q9BSE4
HERPUD2	ENST00000396081.5	TSL:1	c.1064G>T	p.Arg355Leu	missense	Exon 8 of 8	ENSP00000379390.1	Q9BSE4
HERPUD2	ENST00000894710.1		c.1064G>T	p.Arg355Leu	missense	Exon 9 of 9	ENSP00000564769.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249438

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726446

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26046

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

85964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111418

Other (OTH)

AF:

0.00

AC:

AN:

60326

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

Eigen

Benign

0.14

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.019

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

3.3

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.10

Sift

Benign

0.050

Sift4G

Benign

0.62

Polyphen

0.99

Vest4

0.36

MutPred

0.27

Loss of solvent accessibility (P = 0.0238)

MVP

0.39

MPC

0.47

ClinPred

0.75

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.45

Mutation Taster

=43/57

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over