Genetic Variant HERPUD2:p.Val85Ile (chr7-35670301-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_022373.5(HERPUD2):c.253G>A(p.Val85Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000458 in 1,551,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

HERPUD2
NM_022373.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.41

Publications

4 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.

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.253G>A	p.Val85Ile	missense	Exon 4 of 9	NP_071768.3
HERPUD2	NM_001438072.1		c.253G>A	p.Val85Ile	missense	Exon 3 of 8	NP_001425001.1
HERPUD2	NM_001438070.1		c.148-2713G>A		intron	N/A	NP_001424999.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HERPUD2	ENST00000311350.8	TSL:1 MANE Select	c.253G>A	p.Val85Ile	missense	Exon 4 of 9	ENSP00000310729.3	Q9BSE4
HERPUD2	ENST00000396081.5	TSL:1	c.253G>A	p.Val85Ile	missense	Exon 3 of 8	ENSP00000379390.1	Q9BSE4
HERPUD2	ENST00000894710.1		c.253G>A	p.Val85Ile	missense	Exon 4 of 9	ENSP00000564769.1

Frequencies

GnomAD3 genomes

AF:

0.0000674

AC:

AN:

148334

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000874

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000218

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000743

Gnomad OTH

AF:

0.000492

GnomAD2 exomes

AF:

0.0000731

AC:

AN:

232426

AF XY:

0.0000949

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000625

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000838

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.0000435

AC:

AN:

1402912

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

698170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31364

American (AMR)

AF:

0.00

AC:

AN:

41190

Ashkenazi Jewish (ASJ)

AF:

0.000640

AC:

AN:

25008

East Asian (EAS)

AF:

0.00

AC:

AN:

38064

South Asian (SAS)

AF:

0.0000767

AC:

AN:

78240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51800

Middle Eastern (MID)

AF:

0.00321

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.0000177

AC:

AN:

1073724

Other (OTH)

AF:

0.0000345

AC:

AN:

57910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000674

AC:

AN:

148334

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

72028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39964

American (AMR)

AF:

0.00

AC:

AN:

14562

Ashkenazi Jewish (ASJ)

AF:

0.000874

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.000218

AC:

AN:

4582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000743

AC:

AN:

67278

Other (OTH)

AF:

0.000492

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.630

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.028

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.40

MutationAssessor

Pathogenic

3.4

PhyloP100

5.4

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.88

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.59

MutPred

0.53

Loss of catalytic residue at V85 (P = 0.0477)

MVP

0.53

MPC

0.83

ClinPred

0.87

GERP RS

3.8

Varity_R

0.49

gMVP

0.39

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: -26

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over