Genetic Variant ZNF317:p.His180Tyr (chr19-9160183-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020933.5(ZNF317):c.538C>T(p.His180Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,614,178 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H180R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 1 hom. )

Consequence

ZNF317
NM_020933.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.295

Publications

1 publications found

Variant links:

Genes affected

ZNF317 (HGNC:13507): (zinc finger protein 317) 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. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF317 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020303905).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020933.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF317	NM_020933.5	MANE Select	c.538C>T	p.His180Tyr	missense	Exon 7 of 7	NP_065984.3
ZNF317	NM_001190791.2		c.442C>T	p.His148Tyr	missense	Exon 6 of 6	NP_001177720.1	Q96PQ6-2
ZNF317	NR_102435.2		n.972C>T		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF317	ENST00000247956.11	TSL:1 MANE Select	c.538C>T	p.His180Tyr	missense	Exon 7 of 7	ENSP00000247956.5	Q96PQ6-1
ZNF317	ENST00000360385.7	TSL:1	c.442C>T	p.His148Tyr	missense	Exon 6 of 6	ENSP00000353554.2	Q96PQ6-2
ZNF317	ENST00000591278.5	TSL:1	n.*363C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000465780.1	K7EKT9

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000103

AC:

AN:

251320

AF XY:

0.000140

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00136

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000856

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112010

Other (OTH)

AF:

0.0000497

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.0000328

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41556

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000581

AC:

AN:

5166

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

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:

0.0000718

ExAC

AF:

0.0000988

AC:

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

0.082

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.054

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.73

M_CAP

Benign

0.0017

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.29

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.6

REVEL

Benign

0.045

Sift

Benign

0.22

Sift4G

Benign

0.47

Polyphen

0.87

Vest4

0.12

MutPred

0.29

Gain of phosphorylation at H180 (P = 0.0092)

MVP

0.23

MPC

0.77

ClinPred

0.054

GERP RS

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.37

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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