Genetic Variant HERPUD2:p.Ala108Pro (chr7-35670232-C-G) – 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.322G>C(p.Ala108Pro) 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. 15/22 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. A108G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 27)

Failed GnomAD Quality Control

Consequence

HERPUD2
NM_022373.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.963

Publications

40 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:

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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=0.23921287).

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.322G>C	p.Ala108Pro	missense	Exon 4 of 9	NP_071768.3
HERPUD2	NM_001438072.1		c.322G>C	p.Ala108Pro	missense	Exon 3 of 8	NP_001425001.1
HERPUD2	NM_001438070.1		c.148-2644G>C		intron	N/A	NP_001424999.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HERPUD2	ENST00000311350.8	TSL:1 MANE Select	c.322G>C	p.Ala108Pro	missense	Exon 4 of 9	ENSP00000310729.3
HERPUD2	ENST00000396081.5	TSL:1	c.322G>C	p.Ala108Pro	missense	Exon 3 of 8	ENSP00000379390.1
HERPUD2	ENST00000413517.1	TSL:5	c.244G>C	p.Ala82Pro	missense	Exon 2 of 5	ENSP00000391015.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149006

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

149006

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72424

African (AFR)

AF:

0.00

AC:

AN:

40224

American (AMR)

AF:

0.00

AC:

AN:

14780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.00

AC:

AN:

4664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67374

Other (OTH)

AF:

0.00

AC:

AN:

2036

Alfa

AF:

0.00

Hom.:

33030

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0030

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.73

M_CAP

Benign

0.014

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

0.96

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.78

REVEL

Benign

0.046

Sift

Benign

0.086

Sift4G

Benign

0.21

Polyphen

0.93

Vest4

0.13

MutPred

0.17

Gain of glycosylation at A108 (P = 0.0199)

MVP

0.34

MPC

0.37

ClinPred

0.42

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.087

gMVP

0.28

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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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