20-63721274-C-T

Position:

• chr20-63721274-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181485.3(ZGPAT):​c.585-11945C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,694 control chromosomes in the GnomAD database, including 3,707 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 0.19 (3707 hom., cov: 30)
• Consequence: ZGPAT NM_181485.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

Genes affected

ZGPAT (HGNC:15948): (zinc finger CCCH-type and G-patch domain containing) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of epidermal growth factor-activated receptor activity and negative regulation of transcription by RNA polymerase II. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZGPAT	NM_181485.3	c.585-11945C>T		intron_variant		ENST00000355969.11	NP_852150.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZGPAT	ENST00000355969.11	c.585-11945C>T		intron_variant		1	NM_181485.3	ENSP00000348242	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28851 AN: 151576 Hom.: 3709 Cov.: 30

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.190 AC: 28852 AN: 151694 Hom.: 3707 Cov.: 30 AF XY: 0.193 AC XY: 14275 AN XY: 74122

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.192

Alfa AF: 0.190 Hom.: 401

Bravo AF: 0.188

Asia WGS AF: 0.395 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs1291213; hg19: chr20-62352626;