20-63733259-C-G

Variant names:

• chr20-63733259-C-G
• NM_181485.3:c.625C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181485.3(ZGPAT):​c.625C>G​(p.Pro209Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZGPAT NM_181485.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.47

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]

ENSG00000273154 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2780543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZGPAT	NM_181485.3	c.625C>G	p.Pro209Ala	missense_variant	Exon 3 of 7	ENST00000355969.11	NP_852150.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZGPAT	ENST00000355969.11	c.625C>G	p.Pro209Ala	missense_variant	Exon 3 of 7	1	NM_181485.3	ENSP00000348242.6
ENSG00000273154	ENST00000632538.1	c.40C>G	p.Pro14Ala	missense_variant	Exon 1 of 6	3		ENSP00000488802.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.625C>G (p.P209A) alteration is located in exon 3 (coding exon 2) of the ZGPAT gene. This alteration results from a C to G substitution at nucleotide position 625, causing the proline (P) at amino acid position 209 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;.;.;.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	.;.;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M;M;M;M;M
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.1	D;D;D;D;D
REVEL	Benign	0.096
Sift	Benign	0.066	T;T;D;T;D
Sift4G	Uncertain	0.037	D;D;D;D;D
Polyphen		0.90	P;P;P;P;P
Vest4		0.40
MutPred		0.38		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.048
MPC		0.83
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.54
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-62364611;