rs773041798

Variant names:

• chr19-53237592-C-A
• rs773041798
• NM_182609.4:c.1135G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-53237592-C-A
• chr19-53237592-C-G

Variant summary

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

The NM_182609.4(ZNF677):​c.1135G>T​(p.Glu379*) 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 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF677 NM_182609.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 0 publications found

Genes affected

ZNF677 (HGNC:28730): (zinc finger protein 677) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-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]

ENSG00000291131 (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_182609.4. 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
	ZNF677	NM_182609.4	MANE Select	c.1135G>T	p.Glu379*	stop_gained	Exon 5 of 5	NP_872415.1	Q86XU0
	ZNF677	NM_001317998.2		c.1135G>T	p.Glu379*	stop_gained	Exon 5 of 5	NP_001304927.1	Q86XU0
	ZNF677	NM_001385608.1		c.1135G>T	p.Glu379*	stop_gained	Exon 5 of 5	NP_001372537.1	Q86XU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF677	ENST00000598513.6	TSL:1 MANE Select	c.1135G>T	p.Glu379*	stop_gained	Exon 5 of 5	ENSP00000469391.1	Q86XU0
	ZNF677	ENST00000333952.8	TSL:2	c.1135G>T	p.Glu379*	stop_gained	Exon 3 of 3	ENSP00000334394.4	Q86XU0
	ZNF677	ENST00000881288.1		c.1135G>T	p.Glu379*	stop_gained	Exon 5 of 5	ENSP00000551347.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 251016 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461702 Hom.: 0 Cov.: 57 AF XY: 0.00000413 AC XY: 3 AN XY: 727136

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111882

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	32
DANN	Uncertain	0.99
Eigen	Uncertain	0.22
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.0015	N
PhyloP100		-1.3
Vest4		0.041
GERP RS		1.1
Mutation Taster		=132/68	disease causing (fs/PTC)

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: rs773041798; hg19: chr19-53740845;