dbSNP rs12460170: ZNF665:p.Val84Ala (chr19-53166239-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024733.5(ZNF665):c.251T>C(p.Val84Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,613,672 control chromosomes in the GnomAD database, including 305,082 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.52 ( 22946 hom., cov: 32)

Exomes 𝑓: 0.62 ( 282136 hom. )

Consequence

ZNF665
NM_024733.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0270

Variant links:

Genes affected

ZNF665 (HGNC:25885): (zinc finger protein 665) 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]

ZNF665 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1620522E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF665	NM_024733.5 link	c.251T>C	p.Val84Ala	missense_variant	Exon 4 of 4	ENST00000396424.5	NP_079009.3	Q9H7R5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF665	ENST00000396424.5 link	c.251T>C	p.Val84Ala	missense_variant	Exon 4 of 4	2	NM_024733.5	ENSP00000379702.2	Q9H7R5
ZNF665	ENST00000650736.1 link	c.251T>C	p.Val84Ala	missense_variant	Exon 5 of 5			ENSP00000498600.1	Q9H7R5
ZNF665	ENST00000600412.1 link	c.56T>C	p.Val19Ala	missense_variant	Exon 2 of 2	5		ENSP00000469154.1	A0A3Q5AD24

Frequencies

GnomAD3 genomes

AF:

0.516

AC:

78436

AN:

151966

Hom.:

22934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.629

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.655

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.667

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.518

GnomAD3 exomes

AF:

0.624

AC:

155501

AN:

249198

Hom.:

50581

AF XY:

0.629

AC XY:

85090

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.731

Gnomad ASJ exome

AF:

0.496

Gnomad EAS exome

AF:

0.663

Gnomad SAS exome

AF:

0.715

Gnomad FIN exome

AF:

0.677

Gnomad NFE exome

AF:

0.619

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.616

AC:

900457

AN:

1461588

Hom.:

282136

Cov.:

AF XY:

0.620

AC XY:

450496

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.718

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.685

Gnomad4 SAS exome

AF:

0.715

Gnomad4 FIN exome

AF:

0.674

Gnomad4 NFE exome

AF:

0.616

Gnomad4 OTH exome

AF:

0.589

GnomAD4 genome

AF:

0.516

AC:

78477

AN:

152084

Hom.:

22946

Cov.:

AF XY:

0.524

AC XY:

38942

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.616

Gnomad4 ASJ

AF:

0.507

Gnomad4 EAS

AF:

0.655

Gnomad4 SAS

AF:

0.715

Gnomad4 FIN

AF:

0.667

Gnomad4 NFE

AF:

0.620

Gnomad4 OTH

AF:

0.520

Alfa

AF:

0.591

Hom.:

55516

Bravo

AF:

0.496

TwinsUK

AF:

0.611

AC:

2266

ALSPAC

AF:

0.603

AC:

2323

ESP6500AA

AF:

0.224

AC:

870

ESP6500EA

AF:

0.607

AC:

5044

ExAC

AF:

0.617

AC:

74565

EpiCase

AF:

0.606

EpiControl

AF:

0.592

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.2

DANN

Benign

0.21

DEOGEN2

Benign

0.0025

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00096

LIST_S2

Benign

0.0096

T;T

MetaRNN

Benign

0.0000022

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

PrimateAI

Benign

0.20

PROVEAN

Benign

1.5

N;.

REVEL

Benign

0.032

Sift

Benign

0.33

T;.

Sift4G

Benign

0.74

T;T

Polyphen

0.0

B;.

Vest4

0.023

MPC

0.032

ClinPred

0.0065

GERP RS

0.40

Varity_R

0.083

gMVP

0.023

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over