NM_024733.5:c.2021G>C

Variant summary

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

The NM_024733.5(ZNF665):​c.2021G>C​(p.Arg674Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. R674I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

ZNF665
NM_024733.5 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.11
Variant links:
Genes affected
ZNF665 (HGNC:25885): (zinc finger protein 665) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [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=0.14909104).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF665NM_024733.5 linkc.2021G>C p.Arg674Thr missense_variant Exon 4 of 4 ENST00000396424.5 NP_079009.3 Q9H7R5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF665ENST00000396424.5 linkc.2021G>C p.Arg674Thr missense_variant Exon 4 of 4 2 NM_024733.5 ENSP00000379702.2 Q9H7R5
ZNF665ENST00000650736.1 linkc.2021G>C p.Arg674Thr missense_variant Exon 5 of 5 ENSP00000498600.1 Q9H7R5
ZNF665ENST00000600412.1 linkc.1826G>C p.Arg609Thr missense_variant Exon 2 of 2 5 ENSP00000469154.1 A0A3Q5AD24

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.94e-7
AC:
1
AN:
1441870
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
715496
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:
0.00
Gnomad4 NFE exome
AF:
9.07e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.46
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
9.9
DANN
Benign
0.26
DEOGEN2
Benign
0.051
.;T
Eigen
Benign
-0.84
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.0010
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
.;M
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-3.7
D;.
REVEL
Benign
0.033
Sift
Benign
0.041
D;.
Sift4G
Benign
0.20
T;T
Polyphen
0.72
P;.
Vest4
0.16
MutPred
0.56
Loss of MoRF binding (P = 0.0068);.;
MVP
0.23
MPC
0.093
ClinPred
0.33
T
GERP RS
-2.1
Varity_R
0.088
gMVP
0.079

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: chr19-53667722; API