NM_173480.3:c.377A>G

Variant names:

• chr19-2916998-A-G
• NM_173480.3:c.377A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173480.3(ZNF57):​c.377A>G​(p.Asp126Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ZNF57 NM_173480.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.281
• Publications: 0 publications found

Genes affected

ZNF57 (HGNC:13125): (zinc finger protein 57) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253392 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.117440104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173480.3. 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
	ZNF57	NM_173480.3	MANE Select	c.377A>G	p.Asp126Gly	missense	Exon 4 of 4	NP_775751.1	Q68EA5
	ZNF57	NM_001319083.2		c.281A>G	p.Asp94Gly	missense	Exon 4 of 4	NP_001306012.1	G3V131

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF57	ENST00000306908.10	TSL:1 MANE Select	c.377A>G	p.Asp126Gly	missense	Exon 4 of 4	ENSP00000303696.5	Q68EA5
	ZNF57	ENST00000881774.1		c.344A>G	p.Asp115Gly	missense	Exon 4 of 4	ENSP00000551833.1
	ZNF57	ENST00000523428.5	TSL:2	c.281A>G	p.Asp94Gly	missense	Exon 4 of 4	ENSP00000430223.1	G3V131

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.14
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.1
DANN	Benign	0.92
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.073	T
M_CAP	Benign	0.00081	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.28
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.022
Sift	Benign	0.033	D
Sift4G	Benign	0.17	T
Polyphen		0.0040	B
Vest4		0.14
MutPred		0.35		Loss of ubiquitination at K131 (P = 0.0391)
MVP		0.19
MPC		0.035
ClinPred		0.046	T
GERP RS		-2.7
Varity_R		0.055
gMVP		0.023
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

hg19: chr19-2916996;