18-35337626-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006965.4(ZNF24):​c.713G>A​(p.Arg238Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R238T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ZNF24
NM_006965.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76
Variant links:
Genes affected
ZNF24 (HGNC:13032): (zinc finger protein 24) Enables DNA-binding transcription activator activity, RNA polymerase II-specific; identical protein binding activity; and sequence-specific DNA binding activity. Involved in negative regulation of transcription, DNA-templated and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11496243).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF24NM_006965.4 linkc.713G>A p.Arg238Lys missense_variant Exon 4 of 4 ENST00000261332.11 NP_008896.2 P17028-1
ZNF24NM_001375815.1 linkc.713G>A p.Arg238Lys missense_variant Exon 4 of 4 NP_001362744.1
ZNF24NM_001308123.2 linkc.*1434G>A 3_prime_UTR_variant Exon 4 of 4 NP_001295052.1 P17028-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF24ENST00000261332.11 linkc.713G>A p.Arg238Lys missense_variant Exon 4 of 4 1 NM_006965.4 ENSP00000261332.5 P17028-1
ZNF24ENST00000399061.3 linkc.713G>A p.Arg238Lys missense_variant Exon 4 of 4 1 ENSP00000382015.2 P17028-1
ZNF24ENST00000589881 linkc.*1434G>A 3_prime_UTR_variant Exon 3 of 3 1 ENSP00000467655.1 P17028-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251104
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135716
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461794
Hom.:
0
Cov.:
36
AF XY:
0.0000110
AC XY:
8
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000330
AC:
4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.079
T;T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.025
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.15
.;T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.11
Sift
Benign
0.28
T;T
Sift4G
Benign
0.41
T;T
Polyphen
0.83
P;P
Vest4
0.39
MutPred
0.47
Gain of methylation at R238 (P = 0.013);Gain of methylation at R238 (P = 0.013);
MVP
0.30
MPC
0.53
ClinPred
0.36
T
GERP RS
4.5
Varity_R
0.11
gMVP
0.50

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: rs750561326; hg19: chr18-32917590; API