chr11-134250285-C-G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_014174.3(THYN1):​c.281G>C​(p.Arg94Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

THYN1
NM_014174.3 missense

Scores

12
5
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.23

Publications

2 publications found
Variant links:
Genes affected
THYN1 (HGNC:29560): (thymocyte nuclear protein 1) This gene encodes a protein that is highly conserved among vertebrates and plant species and may be involved in the induction of apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
THYN1NM_014174.3 linkc.281G>C p.Arg94Pro missense_variant Exon 3 of 7 ENST00000341541.8 NP_054893.1 Q9P016-1A0A024R3M1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
THYN1ENST00000341541.8 linkc.281G>C p.Arg94Pro missense_variant Exon 3 of 7 1 NM_014174.3 ENSP00000341657.3 Q9P016-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41438
American (AMR)
AF:
0.00
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68018
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.281G>C (p.R94P) alteration is located in exon 3 (coding exon 3) of the THYN1 gene. This alteration results from a G to C substitution at nucleotide position 281, causing the arginine (R) at amino acid position 94 to be replaced by a proline (P). 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.47
D
BayesDel_noAF
Pathogenic
0.43
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.61
D;D;D;.
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
.;.;D;D
M_CAP
Benign
0.071
D
MetaRNN
Pathogenic
0.96
D;D;D;D
MetaSVM
Uncertain
0.63
D
MutationAssessor
Pathogenic
4.7
H;H;H;H
PhyloP100
7.2
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-6.6
D;D;D;D
REVEL
Uncertain
0.55
Sift
Uncertain
0.024
D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.96
MutPred
0.85
Loss of MoRF binding (P = 0.0032);Loss of MoRF binding (P = 0.0032);Loss of MoRF binding (P = 0.0032);Loss of MoRF binding (P = 0.0032);
MVP
0.092
MPC
0.58
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.96
gMVP
0.80
Mutation Taster
=42/58
disease causing

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

Other links and lift over

dbSNP: rs766096798; hg19: chr11-134120179; API