19-55613892-C-T

Variant names:

• chr19-55613892-C-T
• NM_001195605.2:c.274C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195605.2(ZNF865):​c.274C>T​(p.Pro92Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF865 NM_001195605.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.558
• Publications: 0 publications found

Genes affected

ZNF865 (HGNC:38705): (zinc finger protein 865) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19097751).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195605.2. 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
	ZNF865	NM_001195605.2	MANE Select	c.274C>T	p.Pro92Ser	missense	Exon 2 of 2	NP_001182534.1	P0CJ78

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF865	ENST00000568956.2	TSL:2 MANE Select	c.274C>T	p.Pro92Ser	missense	Exon 2 of 2	ENSP00000457715.1	P0CJ78
	ZNF865	ENST00000870148.1		c.274C>T	p.Pro92Ser	missense	Exon 3 of 3	ENSP00000540207.1
	ZNF865	ENST00000870149.1		c.274C>T	p.Pro92Ser	missense	Exon 2 of 2	ENSP00000540208.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1297112 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 641160

African (AFR) AF: 0.00 AC: 0 AN: 28772

American (AMR) AF: 0.00 AC: 0 AN: 33526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22504

East Asian (EAS) AF: 0.00 AC: 0 AN: 30346

South Asian (SAS) AF: 0.00 AC: 0 AN: 77910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5338

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1017914

Other (OTH) AF: 0.00 AC: 0 AN: 53038

GnomAD4 genome Cov.: 30

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	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.19	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.56
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.69	N
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.0040	D
Vest4		0.21
MVP		0.42
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
gMVP		0.14
Mutation Taster		=90/10	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: chr19-56125258;