Genetic Variant ZNF865:p.Thr319Met (chr19-55614574-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195605.2(ZNF865):c.956C>T(p.Thr319Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,504,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ZNF865
NM_001195605.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0440

Publications

0 publications found

Variant links:

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]

ZNF865 links:

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ACMG classification

Classification was made for transcript

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=0.15221494).

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.956C>T	p.Thr319Met	missense	Exon 2 of 2	NP_001182534.1	P0CJ78

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF865	ENST00000568956.2	TSL:2 MANE Select	c.956C>T	p.Thr319Met	missense	Exon 2 of 2	ENSP00000457715.1	P0CJ78
ZNF865	ENST00000870148.1		c.956C>T	p.Thr319Met	missense	Exon 3 of 3	ENSP00000540207.1
ZNF865	ENST00000870149.1		c.956C>T	p.Thr319Met	missense	Exon 2 of 2	ENSP00000540208.1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

101002

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000281

AC:

AN:

1352850

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

666766

show subpopulations

African (AFR)

AF:

0.0000344

AC:

AN:

29108

American (AMR)

AF:

0.00

AC:

AN:

31918

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23414

East Asian (EAS)

AF:

0.00

AC:

AN:

33272

South Asian (SAS)

AF:

0.00

AC:

AN:

75254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5524

European-Non Finnish (NFE)

AF:

0.0000338

AC:

AN:

1064912

Other (OTH)

AF:

0.0000177

AC:

AN:

56602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151674

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74078

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41372

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67922

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.013

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.15

MutationAssessor

Benign

0.69

PhyloP100

0.044

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.16

Sift

Benign

0.23

Sift4G

Benign

0.32

Vest4

0.24

MVP

0.53

GERP RS

3.1

Varity_R

0.033

gMVP

0.18

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over