1-42851623-G-A

Variant summary

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

The NM_001242739.2(ZNF691):​c.758G>A​(p.Arg253Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,892 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

ZNF691
NM_001242739.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.920
Variant links:
Genes affected
ZNF691 (HGNC:28028): (zinc finger protein 691) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.03424725).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF691NM_001242739.2 linkuse as main transcriptc.758G>A p.Arg253Lys missense_variant 4/4 ENST00000651192.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF691ENST00000651192.1 linkuse as main transcriptc.758G>A p.Arg253Lys missense_variant 4/4 NM_001242739.2 Q5VV52-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152010
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000677
AC:
17
AN:
251194
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000392
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000383
AC:
56
AN:
1461882
Hom.:
1
Cov.:
31
AF XY:
0.0000495
AC XY:
36
AN XY:
727244
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:
0.000452
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152010
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000741
AC:
9

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 13, 2021The c.758G>A (p.R253K) alteration is located in exon 4 (coding exon 2) of the ZNF691 gene. This alteration results from a G to A substitution at nucleotide position 758, causing the arginine (R) at amino acid position 253 to be replaced by a lysine (K). 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
0.24
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
18
DANN
Benign
0.97
DEOGEN2
Benign
0.018
T;.;.;.;T;T;T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.089
FATHMM_MKL
Benign
0.47
N
LIST_S2
Benign
0.074
T;.;.;T;.;T;T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.034
T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-1.6
N;.;.;.;.;.;.
MutationTaster
Benign
0.90
N;N;N;N;N;N;N
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
1.7
N;N;N;N;N;N;.
REVEL
Benign
0.15
Sift
Benign
1.0
T;T;T;T;T;T;.
Sift4G
Benign
1.0
T;T;T;T;T;T;T
Polyphen
0.40
B;.;.;.;.;.;.
Vest4
0.17
MutPred
0.46
Gain of methylation at R253 (P = 0.0052);.;.;.;.;Gain of methylation at R253 (P = 0.0052);.;
MVP
0.067
ClinPred
0.077
T
GERP RS
5.1
Varity_R
0.072
gMVP
0.15

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: rs749840780; hg19: chr1-43317294; API