Variant chr7-35670253-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022373.5(HERPUD2):c.301A>G(p.Arg101Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00009 in 1,588,184 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

HERPUD2
NM_022373.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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 made for transcript

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=0.027376086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERPUD2	NM_022373.5 linkuse as main transcript	c.301A>G	p.Arg101Gly	missense_variant	4/9	ENST00000311350.8	NP_071768.3	Q9BSE4A0A024RA77

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERPUD2	ENST00000311350.8 linkuse as main transcript	c.301A>G	p.Arg101Gly	missense_variant	4/9	1	NM_022373.5	ENSP00000310729.3		Q9BSE4

Frequencies

GnomAD3 genomes

AF:

0.0000802

AC:

AN:

149594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000135

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:

0.0000889

Gnomad OTH

AF:

0.000977

GnomAD3 exomes

AF:

0.000140

AC:

AN:

243036

Hom.:

AF XY:

0.000159

AC XY:

AN XY:

131706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000402

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

AF:

0.0000911

AC:

131

AN:

1438472

Hom.:

Cov.:

AF XY:

0.0000950

AC XY:

AN XY:

715980

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000483

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000802

Gnomad4 OTH exome

AF:

0.000303

GnomAD4 genome

AF:

0.0000802

AC:

AN:

149712

Hom.:

Cov.:

AF XY:

0.0000685

AC XY:

AN XY:

72954

show subpopulations

Gnomad4 AFR

AF:

0.0000493

Gnomad4 AMR

AF:

0.000135

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000889

Gnomad4 OTH

AF:

0.000966

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000151

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.301A>G (p.R101G) alteration is located in exon 4 (coding exon 3) of the HERPUD2 gene. This alteration results from a A to G substitution at nucleotide position 301, causing the arginine (R) at amino acid position 101 to be replaced by a glycine (G). 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

0.067

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.0063

T;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.72

.;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.37

T;T;T

Sift4G

Benign

0.37

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.13

MVP

0.24

MPC

0.37

ClinPred

0.026

GERP RS

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.090

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over