NM_001009931.3:c.8030G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001009931.3(HRNR):​c.8030G>T​(p.Arg2677Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 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. R2677P) has been classified as Benign.

Frequency

Genomes: not found (cov: 10)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

HRNR
NM_001009931.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25
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]
CCDST (HGNC:55988): (cervical cancer associated DHX9 suppressive transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.091379225).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HRNRNM_001009931.3 linkc.8030G>T p.Arg2677Leu missense_variant Exon 3 of 3 ENST00000368801.4 NP_001009931.1 Q86YZ3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HRNRENST00000368801.4 linkc.8030G>T p.Arg2677Leu missense_variant Exon 3 of 3 1 NM_001009931.3 ENSP00000357791.3 Q86YZ3

Frequencies

GnomAD3 genomes
Cov.:
10
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000274
AC:
3
AN:
1094524
Hom.:
0
Cov.:
31
AF XY:
0.00000182
AC XY:
1
AN XY:
549672
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000221
Gnomad4 NFE exome
AF:
0.00000245
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
10
ExAC
AF:
0.00000973
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
3.6
DANN
Benign
0.61
DEOGEN2
Benign
0.023
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0085
N
LIST_S2
Benign
0.30
T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.091
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.55
N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.015
Sift
Benign
0.052
T
Sift4G
Uncertain
0.058
T
Polyphen
0.10
B
Vest4
0.23
MutPred
0.31
Loss of MoRF binding (P = 0.0021);
MVP
0.25
ClinPred
0.063
T
GERP RS
-0.93
Varity_R
0.057
gMVP
0.036

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

LitVar

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

Other links and lift over

dbSNP: rs201827906; hg19: chr1-152186075; API