chr16-25240087-C-T

Variant names:

• chr16-25240087-C-T
• rs61742943
• NM_001012981.5:c.2633G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 15/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00900
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012981.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN2	NM_001012981.5	MANE Select	c.2633G>A	p.Arg878Gln	missense	Exon 7 of 7	NP_001012999.3	Q63HK3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN2	ENST00000328086.12	TSL:1 MANE Select	c.2633G>A	p.Arg878Gln	missense	Exon 7 of 7	ENSP00000331626.7	Q63HK3-1
	ZKSCAN2	ENST00000919970.1		c.2141G>A	p.Arg714Gln	missense	Exon 6 of 6	ENSP00000590029.1
	ZKSCAN2	ENST00000964638.1		c.1457G>A	p.Arg486Gln	missense	Exon 5 of 5	ENSP00000634697.1

Frequencies

GnomAD3 genomes AF: 0.000502 AC: 76 AN: 151438 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000501 AC: 126 AN: 251316 AF XY: 0.000479

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 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

African (AFR) AF: 0.000179 AC: 6 AN: 33478

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86256

European-Finnish (FIN) AF: 0.000188 AC: 10 AN: 53234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000561 AC: 624 AN: 1111978

Other (OTH) AF: 0.000364 AC: 22 AN: 60396

GnomAD4 genome AF: 0.000502 AC: 76 AN: 151438 Hom.: 0 Cov.: 32 AF XY: 0.000473 AC XY: 35 AN XY: 73958

African (AFR) AF: 0.000121 AC: 5 AN: 41172

American (AMR) AF: 0.000197 AC: 3 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4744

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000943 AC: 64 AN: 67836

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.000721 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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.0090
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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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