19-2916198-T-A

Variant names:

• chr19-2916198-T-A
• rs2088192931
• NM_173480.3:c.251T>A

Variant summary

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

The NM_173480.3(ZNF57):​c.251T>A​(p.Leu84*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,006 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF57 NM_173480.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• 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 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.251T>A	p.Leu84*	stop_gained	Exon 3 of 4	NP_775751.1	Q68EA5
	ZNF57	NM_001319083.2		c.155T>A	p.Leu52*	stop_gained	Exon 3 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.251T>A	p.Leu84*	stop_gained	Exon 3 of 4	ENSP00000303696.5	Q68EA5
	ZNF57	ENST00000881774.1		c.218T>A	p.Leu73*	stop_gained	Exon 3 of 4	ENSP00000551833.1
	ZNF57	ENST00000523428.5	TSL:2	c.155T>A	p.Leu52*	stop_gained	Exon 3 of 4	ENSP00000430223.1	G3V131

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461006 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726812

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111728

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	33
DANN	Benign	0.96
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.017	N
PhyloP100		0.14
Vest4		0.029
GERP RS		0.17
Mutation Taster		=195/5	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

dbSNP: rs2088192931; hg19: chr19-2916196;