1-152409971-C-T

Variant summary

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

The NM_016190.3(CRNN):​c.1111G>A​(p.Ala371Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CRNN
NM_016190.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.36
Variant links:
Genes affected
CRNN (HGNC:1230): (cornulin) This gene encodes a member of the "fused gene" family of proteins, which contain N-terminus EF-hand domains and multiple tandem peptide repeats. The encoded protein contains two EF-hand Ca2+ binding domains in its N-terminus and two glutamine- and threonine-rich 60 amino acid repeats in its C-terminus. This gene, also known as squamous epithelial heat shock protein 53, may play a role in the mucosal/epithelial immune response and epidermal differentiation. [provided by RefSeq, Jan 2009]

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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=0.043438137).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRNNNM_016190.3 linkc.1111G>A p.Ala371Thr missense_variant Exon 3 of 3 ENST00000271835.3 NP_057274.1 Q9UBG3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRNNENST00000271835.3 linkc.1111G>A p.Ala371Thr missense_variant Exon 3 of 3 1 NM_016190.3 ENSP00000271835.3 Q9UBG3
FLG-AS1ENST00000411804.1 linkn.95-34873C>T intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1111G>A (p.A371T) alteration is located in exon 3 (coding exon 2) of the CRNN gene. This alteration results from a G to A substitution at nucleotide position 1111, causing the alanine (A) at amino acid position 371 to be replaced by a threonine (T). 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
0.068
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.23
DANN
Benign
0.66
DEOGEN2
Benign
0.0015
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0098
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.043
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.32
N
REVEL
Benign
0.021
Sift
Benign
0.072
T
Sift4G
Benign
0.36
T
Polyphen
0.13
B
Vest4
0.024
MutPred
0.19
Gain of glycosylation at A371 (P = 0.0303);
MVP
0.040
MPC
0.067
ClinPred
0.047
T
GERP RS
-0.98
Varity_R
0.032
gMVP
0.064

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-152382447; API