19-2933988-T-G

Position:

• chr19-2933988-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000314531.5(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 ENST00000314531.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0720

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF77	NM_021217.3	c.1139A>C	p.Tyr380Ser	missense_variant	4/4	ENST00000314531.5	NP_067040.1
ZNF77	XM_047439170.1	c.1043A>C	p.Tyr348Ser	missense_variant	4/4		XP_047295126.1
ZNF77	XM_017027081.2	c.599A>C	p.Tyr200Ser	missense_variant	3/3		XP_016882570.1
ZNF77	XM_047439171.1	c.599A>C	p.Tyr200Ser	missense_variant	3/3		XP_047295127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF77	ENST00000314531.5	c.1139A>C	p.Tyr380Ser	missense_variant	4/4	1	NM_021217.3	ENSP00000319053	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 79

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 07, 2024

The c.1139A>C (p.Y380S) alteration is located in exon 4 (coding exon 4) of the ZNF77 gene. This alteration results from a A to C substitution at nucleotide position 1139, causing the tyrosine (Y) at amino acid position 380 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	N
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-2933986;