rs193921007

Variant names:

• chr19-57753704-A-C
• rs193921007
• NM_173632.4:c.574A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-57753704-A-C
• chr19-57753704-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173632.4(ZNF776):​c.574A>C​(p.Asn192His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF776 NM_173632.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.341
• Publications: 0 publications found

Genes affected

ZNF776 (HGNC:26765): (zinc finger protein 776) 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]

ENSG00000269026 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064831644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173632.4. 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
	ZNF776	NM_173632.4	MANE Select	c.574A>C	p.Asn192His	missense	Exon 3 of 3	NP_775903.3
	ZNF776	NM_001348007.2		c.249+325A>C		intron	N/A	NP_001334936.1
	ZNF776	NR_145326.2		n.818A>C		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF776	ENST00000317178.10	TSL:1 MANE Select	c.574A>C	p.Asn192His	missense	Exon 3 of 3	ENSP00000321812.5	Q68DI1
	ZNF776	ENST00000451849.1	TSL:3	c.106+2793A>C		intron	N/A	ENSP00000416901.1	H7C4D2
	ENSG00000269026	ENST00000594684.1	TSL:1	c.*129A>C		downstream_gene	N/A	ENSP00000472160.1	M0R1X1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.4
DANN	Benign	0.64
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.036	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.56	N
PhyloP100		0.34
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.010
Sift	Benign	0.18	T
Sift4G	Benign	0.34	T
Polyphen		0.010	B
Vest4		0.18
MutPred		0.35		Gain of disorder (P = 0.0866)
MVP		0.16
MPC		0.37
ClinPred		0.087	T
GERP RS		-2.8
Varity_R		0.093
gMVP		0.017
Mutation Taster		=100/0	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: rs193921007; hg19: chr19-58265072; COSMIC: COSV57814757; COSMIC: COSV57814757;