rs199689984

Variant names:

• chr19-7083159-C-G
• rs199689984
• NM_024341.3:c.708C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-7083159-C-G
• chr19-7083159-C-T

Variant summary

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

The NM_024341.3(ZNF557):​c.708C>G​(p.Tyr236*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y236Y) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF557 NM_024341.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 0 publications found

Genes affected

ZNF557 (HGNC:28632): (zinc finger protein 557) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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_024341.3. 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
	ZNF557	NM_024341.3	MANE Select	c.708C>G	p.Tyr236*	stop_gained	Exon 8 of 8	NP_077317.2	Q8N988-2
	ZNF557	NM_001044387.2		c.708C>G	p.Tyr236*	stop_gained	Exon 8 of 8	NP_001037852.1	Q8N988-2
	ZNF557	NM_001044388.2		c.687C>G	p.Tyr229*	stop_gained	Exon 8 of 8	NP_001037853.1	Q8N988-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF557	ENST00000252840.11	TSL:1 MANE Select	c.708C>G	p.Tyr236*	stop_gained	Exon 8 of 8	ENSP00000252840.5	Q8N988-2
	ZNF557	ENST00000882902.1		c.708C>G	p.Tyr236*	stop_gained	Exon 8 of 8	ENSP00000552961.1
	ZNF557	ENST00000882905.1		c.708C>G	p.Tyr236*	stop_gained	Exon 9 of 9	ENSP00000552964.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

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

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111998

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Benign	0.93
Eigen	Benign	-0.78
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0	N
PhyloP100		-2.2
Vest4		0.025
GERP RS		-1.8
Mutation Taster		=172/28	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: rs199689984; hg19: chr19-7083170;