chr11-76351044-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_004705.4(THAP12):​c.2106G>A​(p.Lys702Lys) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

THAP12
NM_004705.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.235

Publications

0 publications found
Variant links:
Genes affected
THAP12 (HGNC:9440): (THAP domain containing 12) Predicted to enable DNA binding activity; metal ion binding activity; and protein dimerization activity. Predicted to be involved in negative regulation of cell population proliferation and signal transduction. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
THAP12 Gene-Disease associations (from GenCC):
  • syndromic complex neurodevelopmental disorder
    Inheritance: AR Classification: LIMITED Submitted by: Broad Center for Mendelian Genomics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 11-76351044-C-T is Benign according to our data. Variant chr11-76351044-C-T is described in CliVar as Likely_benign. Clinvar id is 2642165.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-76351044-C-T is described in CliVar as Likely_benign. Clinvar id is 2642165.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-76351044-C-T is described in CliVar as Likely_benign. Clinvar id is 2642165.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-76351044-C-T is described in CliVar as Likely_benign. Clinvar id is 2642165.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.235 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
THAP12NM_004705.4 linkc.2106G>A p.Lys702Lys synonymous_variant Exon 5 of 5 ENST00000260045.8 NP_004696.2 O43422-1A0A140VJQ7
THAP12NR_130898.2 linkn.2497G>A non_coding_transcript_exon_variant Exon 6 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
THAP12ENST00000260045.8 linkc.2106G>A p.Lys702Lys synonymous_variant Exon 5 of 5 1 NM_004705.4 ENSP00000260045.3 O43422-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.0000160
AC:
4
AN:
250748
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.000186
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000997
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000480
AC:
7
AN:
1459244
Hom.:
0
Cov.:
31
AF XY:
0.00000551
AC XY:
4
AN XY:
725948
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000301
AC:
1
AN:
33266
American (AMR)
AF:
0.00
AC:
0
AN:
44678
Ashkenazi Jewish (ASJ)
AF:
0.0000384
AC:
1
AN:
26050
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86160
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4126
European-Non Finnish (NFE)
AF:
0.00000360
AC:
4
AN:
1111680
Other (OTH)
AF:
0.00
AC:
0
AN:
60166
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.254
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000492
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Nov 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

THAP12: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
2.0
DANN
Benign
0.55
PhyloP100
0.23

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: rs752359040; hg19: chr11-76062088; COSMIC: COSV52611006; COSMIC: COSV52611006; API