NM_001012981.5:c.2633G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001012981.5(ZKSCAN2):​c.2633G>A​(p.Arg878Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,613,104 control chromosomes in the GnomAD database, including 3 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 0.00050 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00046 ( 3 hom. )

Consequence

ZKSCAN2
NM_001012981.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00900
Variant links:
Genes affected
ZKSCAN2 (HGNC:25677): (zinc finger with KRAB and SCAN domains 2) 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 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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.026019454).
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZKSCAN2NM_001012981.5 linkc.2633G>A p.Arg878Gln missense_variant Exon 7 of 7 ENST00000328086.12 NP_001012999.3 Q63HK3-1
ZKSCAN2XM_017023200.3 linkc.2021G>A p.Arg674Gln missense_variant Exon 6 of 6 XP_016878689.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZKSCAN2ENST00000328086.12 linkc.2633G>A p.Arg878Gln missense_variant Exon 7 of 7 1 NM_001012981.5 ENSP00000331626.7 Q63HK3-1
ZKSCAN2ENST00000569150.1 linkn.*1945G>A non_coding_transcript_exon_variant Exon 7 of 7 2 ENSP00000455586.1 H3BQ35
ZKSCAN2ENST00000569150.1 linkn.*1945G>A 3_prime_UTR_variant Exon 7 of 7 2 ENSP00000455586.1 H3BQ35

Frequencies

GnomAD3 genomes
AF:
0.000502
AC:
76
AN:
151438
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000211
Gnomad FIN
AF:
0.000284
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000943
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000501
AC:
126
AN:
251316
Hom.:
1
AF XY:
0.000479
AC XY:
65
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.00101
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000465
AC:
679
AN:
1461666
Hom.:
3
Cov.:
31
AF XY:
0.000466
AC XY:
339
AN XY:
727156
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.000188
Gnomad4 NFE exome
AF:
0.000561
Gnomad4 OTH exome
AF:
0.000364
GnomAD4 genome
AF:
0.000502
AC:
76
AN:
151438
Hom.:
0
Cov.:
32
AF XY:
0.000473
AC XY:
35
AN XY:
73958
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.000197
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000211
Gnomad4 FIN
AF:
0.000284
Gnomad4 NFE
AF:
0.000943
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000755
Hom.:
0
Bravo
AF:
0.000348
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000228
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000544
AC:
66
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000533

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 16, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2633G>A (p.R878Q) alteration is located in exon 7 (coding exon 7) of the ZKSCAN2 gene. This alteration results from a G to A substitution at nucleotide position 2633, causing the arginine (R) at amino acid position 878 to be replaced by a glutamine (Q). 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
0.091
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.00087
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.026
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.28
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.19
N
REVEL
Benign
0.032
Sift
Benign
0.62
T
Sift4G
Benign
0.72
T
Polyphen
0.039
B
Vest4
0.089
MVP
0.048
MPC
0.20
ClinPred
0.0075
T
GERP RS
2.7
Varity_R
0.054
gMVP
0.28

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: rs61742943; hg19: chr16-25251408; COSMIC: COSV60156684; COSMIC: COSV60156684; API