chr19-2933988-T-G

Variant names:

• chr19-2933988-T-G
• NM_021217.3:c.1139A>C

Variant summary

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

The NM_021217.3(ZNF77):​c.1139A>C​(p.Tyr380Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF77 NM_021217.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0720
• Publications: 0 publications found

Genes affected

ZNF77 (HGNC:13150): (zinc finger protein 77) 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_021217.3. 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
	ZNF77	NM_021217.3	MANE Select	c.1139A>C	p.Tyr380Ser	missense	Exon 4 of 4	NP_067040.1	Q15935
	ZNF77	NM_001426550.1		c.599A>C	p.Tyr200Ser	missense	Exon 3 of 3	NP_001413479.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF77	ENST00000314531.5	TSL:1 MANE Select	c.1139A>C	p.Tyr380Ser	missense	Exon 4 of 4	ENSP00000319053.3	Q15935
	ZNF77	ENST00000915162.1		c.1136A>C	p.Tyr379Ser	missense	Exon 4 of 4	ENSP00000585221.1
	ZNF77	ENST00000863233.1		c.515A>C	p.Tyr172Ser	missense	Exon 4 of 4	ENSP00000533292.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 79

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	Pathogenic	0.82
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.00019	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.072
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-8.1	D
REVEL	Benign	0.061
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.31
MutPred		0.60		Gain of disorder (P = 0.0113)
MVP		0.40
MPC		0.35
ClinPred		0.98	D
GERP RS		0.72
Varity_R		0.62
gMVP		0.10
Mutation Taster		=99/1	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: chr19-2933986;