20-63708869-C-G

Variant names:

• chr20-63708869-C-G
• rs374989957
• NM_181485.3:c.289C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181485.3(ZGPAT):​c.289C>G​(p.Arg97Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,609,416 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: ZGPAT NM_181485.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.448
• Publications: 0 publications found

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:):

ARFRP1 (HGNC:662): (ADP ribosylation factor related protein 1) The protein encoded by this gene is a membrane-associated GTP-ase which localizes to the plasma membrane and is related to the ADP-ribosylation factor (ARF) and ARF-like (ARL) proteins. This gene plays a role in membrane trafficking between the trans-Golgi network and endosomes. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023446232).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181485.3. 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
	ZGPAT	NM_181485.3	MANE Select	c.289C>G	p.Arg97Gly	missense	Exon 2 of 7	NP_852150.2	A0A0S2Z5X3
	ZGPAT	NM_032527.5		c.289C>G	p.Arg97Gly	missense	Exon 2 of 7	NP_115916.3
	ZGPAT	NM_001083113.2		c.289C>G	p.Arg97Gly	missense	Exon 2 of 7	NP_001076582.1	A0A0S2Z5X3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZGPAT	ENST00000355969.11	TSL:1 MANE Select	c.289C>G	p.Arg97Gly	missense	Exon 2 of 7	ENSP00000348242.6	Q8N5A5-2
	ZGPAT	ENST00000448100.6	TSL:1	c.289C>G	p.Arg97Gly	missense	Exon 2 of 7	ENSP00000391176.1	Q8N5A5-2
	ZGPAT	ENST00000357119.8	TSL:1	c.289C>G	p.Arg97Gly	missense	Exon 2 of 7	ENSP00000349634.4	Q8N5A5-3

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000276 AC: 68 AN: 246358 AF XY: 0.000329

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000144

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000223 AC: 325 AN: 1457214 Hom.: 1 Cov.: 35 AF XY: 0.000260 AC XY: 188 AN XY: 724418

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.000135 AC: 6 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00198 AC: 51 AN: 25800

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39662

South Asian (SAS) AF: 0.000957 AC: 82 AN: 85696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52200

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5758

European-Non Finnish (NFE) AF: 0.000144 AC: 160 AN: 1109854

Other (OTH) AF: 0.000332 AC: 20 AN: 60226

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41444

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000827 AC: 4 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000404 Hom.: 0

Bravo AF: 0.000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.000255 AC: 31

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	0.052
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.57
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.45
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.028
Sift	Benign	0.21	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.14
MVP		0.061
MPC		0.33
ClinPred		0.0044	T
GERP RS		1.3
Varity_R		0.19
gMVP		0.24
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs374989957; hg19: chr20-62340221;