Genetic Variant HRNR:p.Ser2184Arg (chr1-152215077-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001009931.3(HRNR):c.6552C>A(p.Ser2184Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Synonymous variant affecting the same amino acid position (i.e. S2184S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 35)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HRNR
NM_001009931.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.734

Publications

0 publications found

Variant links:

Genes affected

HRNR (HGNC:20846): (hornerin) Predicted to enable calcium ion binding activity and transition metal ion binding activity. Involved in cell envelope organization and establishment of skin barrier. Located in cornified envelope; keratohyalin granule; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

HRNR links:

CCDST (HGNC:55988): (cervical cancer associated DHX9 suppressive transcript)

CCDST links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10935533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009931.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HRNR	NM_001009931.3	MANE Select	c.6552C>A	p.Ser2184Arg	missense	Exon 3 of 3	NP_001009931.1	Q86YZ3
CCDST	NR_186761.1		n.353+25422G>T		intron	N/A
CCDST	NR_186762.1		n.179+25596G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HRNR	ENST00000368801.4	TSL:1 MANE Select	c.6552C>A	p.Ser2184Arg	missense	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
CCDST	ENST00000420707.5	TSL:5	n.158+25569G>T		intron	N/A
CCDST	ENST00000593011.5	TSL:4	n.296+46657G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

135416

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

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

AF:

0.00

AC:

AN:

1455946

Hom.:

Cov.:

126

AF XY:

0.00

AC XY:

AN XY:

724424

African (AFR)

AF:

0.00

AC:

AN:

32294

American (AMR)

AF:

0.00

AC:

AN:

44264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

85930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52714

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109210

Other (OTH)

AF:

0.00

AC:

AN:

60128

GnomAD4 genome

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

AF:

0.00

AC:

AN:

135494

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66300

African (AFR)

AF:

0.00

AC:

AN:

32976

American (AMR)

AF:

0.00

AC:

AN:

14008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3296

East Asian (EAS)

AF:

0.00

AC:

AN:

4442

South Asian (SAS)

AF:

0.00

AC:

AN:

4322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

188

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63676

Other (OTH)

AF:

0.00

AC:

AN:

1858

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

4.8

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.018

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.21

M_CAP

Benign

0.0014

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.0

PhyloP100

-0.73

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.7

REVEL

Benign

0.019

Sift

Uncertain

0.021

Sift4G

Uncertain

0.027

Polyphen

0.053

Vest4

0.23

MutPred

0.34

Loss of phosphorylation at S2184 (P = 7e-04)

MVP

0.16

ClinPred

0.055

GERP RS

-3.1

Varity_R

0.078

gMVP

0.043

Mutation Taster

=100/0

polymorphism

(source)

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

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