19-2917095-C-G

Variant names:

• chr19-2917095-C-G
• rs190426178
• NM_173480.3:c.474C>G

Variant summary

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

The NM_173480.3(ZNF57):​c.474C>G​(p.His158Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF57 NM_173480.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 3 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.474C>G	p.His158Gln	missense	Exon 4 of 4	NP_775751.1	Q68EA5
	ZNF57	NM_001319083.2		c.378C>G	p.His126Gln	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.474C>G	p.His158Gln	missense	Exon 4 of 4	ENSP00000303696.5	Q68EA5
	ZNF57	ENST00000881774.1		c.441C>G	p.His147Gln	missense	Exon 4 of 4	ENSP00000551833.1
	ZNF57	ENST00000523428.5	TSL:2	c.378C>G	p.His126Gln	missense	Exon 4 of 4	ENSP00000430223.1	G3V131

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251356 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461798 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111940

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	1.4
DANN	Benign	0.82
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Pathogenic	1.4	D
MutationAssessor	Pathogenic	4.2	H
PhyloP100		-2.2
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.026	D
Polyphen		0.96	D
Vest4		0.21
MutPred		0.68		Gain of MoRF binding (P = 0.0911)
MVP		0.88
MPC		0.040
ClinPred		0.43	T
GERP RS		-3.8
Varity_R		0.17
gMVP		0.049
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs190426178; hg19: chr19-2917093;