6-28245461-T-C

Variant names:

• chr6-28245461-T-C
• rs1150712
• NM_019110.5:c.1293A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_019110.5(ZKSCAN4):​c.1293A>G​(p.Pro431Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,614,190 control chromosomes in the GnomAD database, including 1,615 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.045 (346 hom., cov: 32)
  • Exomes 𝑓: 0.015 (1269 hom.)
• Consequence: ZKSCAN4 NM_019110.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 6 publications found

Genes affected

ZKSCAN4 (HGNC:13854): (zinc finger with KRAB and SCAN domains 4) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-2.69 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN4	NM_019110.5	c.1293A>G	p.Pro431Pro	synonymous_variant	Exon 5 of 5	ENST00000377294.3	NP_061983.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN4	ENST00000377294.3	c.1293A>G	p.Pro431Pro	synonymous_variant	Exon 5 of 5	1	NM_019110.5	ENSP00000366509.2

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6803 AN: 152184 Hom.: 346 Cov.: 32

Gnomad AFR AF: 0.0953

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00350

Gnomad OTH AF: 0.0320

GnomAD2 exomes AF: 0.0421 AC: 10593 AN: 251414 AF XY: 0.0368

Gnomad AFR exome AF: 0.0987

Gnomad AMR exome AF: 0.0919

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.225

Gnomad FIN exome AF: 0.0134

Gnomad NFE exome AF: 0.00385

Gnomad OTH exome AF: 0.0233

GnomAD4 exome AF: 0.0151 AC: 22124 AN: 1461888 Hom.: 1269 Cov.: 32 AF XY: 0.0150 AC XY: 10907 AN XY: 727248

African (AFR) AF: 0.0953 AC: 3190 AN: 33480

American (AMR) AF: 0.0862 AC: 3855 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0114 AC: 298 AN: 26136

East Asian (EAS) AF: 0.202 AC: 8021 AN: 39700

South Asian (SAS) AF: 0.0241 AC: 2079 AN: 86258

European-Finnish (FIN) AF: 0.0127 AC: 676 AN: 53420

Middle Eastern (MID) AF: 0.0269 AC: 155 AN: 5768

European-Non Finnish (NFE) AF: 0.00223 AC: 2483 AN: 1112008

Other (OTH) AF: 0.0226 AC: 1367 AN: 60396

GnomAD4 genome AF: 0.0447 AC: 6808 AN: 152302 Hom.: 346 Cov.: 32 AF XY: 0.0464 AC XY: 3452 AN XY: 74468

African (AFR) AF: 0.0952 AC: 3955 AN: 41560

American (AMR) AF: 0.0720 AC: 1102 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1081 AN: 5170

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4826

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00350 AC: 238 AN: 68030

Other (OTH) AF: 0.0312 AC: 66 AN: 2116

Alfa AF: 0.0209 Hom.: 248

Bravo AF: 0.0544

Asia WGS AF: 0.0680 AC: 235 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.17
DANN	Benign	0.62
PhyloP100		-2.7
Mutation Taster		=98/2	polymorphism (auto)

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: rs1150712; hg19: chr6-28213239; COSMIC: COSV66023131;