Variant 19-53164551-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024733.5(ZNF665):c.1939G>A(p.Val647Ile) 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 1,613,352 control chromosomes in the GnomAD database, including 305,094 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.52 ( 22966 hom., cov: 33)

Exomes 𝑓: 0.62 ( 282128 hom. )

Consequence

ZNF665
NM_024733.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

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=3.0616925E-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/exons	MANE	Protein	UniProt
ZNF665	NM_024733.5 linkuse as main transcript	c.1939G>A	p.Val647Ile	missense_variant	4/4	ENST00000396424.5	NP_079009.3	Q9H7R5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF665	ENST00000396424.5 linkuse as main transcript	c.1939G>A	p.Val647Ile	missense_variant	4/4	2	NM_024733.5	ENSP00000379702.2	Q9H7R5
ZNF665	ENST00000650736.1 linkuse as main transcript	c.1939G>A	p.Val647Ile	missense_variant	5/5			ENSP00000498600.1	Q9H7R5
ZNF665	ENST00000600412.1 linkuse as main transcript	c.1744G>A	p.Val582Ile	missense_variant	2/2	5		ENSP00000469154.1	A0A3Q5AD24

Frequencies

GnomAD3 genomes

AF:

0.517

AC:

78466

AN:

151860

Hom.:

22955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.632

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.655

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.520

GnomAD3 exomes

AF:

0.623

AC:

156233

AN:

250650

Hom.:

50803

AF XY:

0.629

AC XY:

85420

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.731

Gnomad ASJ exome

AF:

0.496

Gnomad EAS exome

AF:

0.661

Gnomad SAS exome

AF:

0.715

Gnomad FIN exome

AF:

0.677

Gnomad NFE exome

AF:

0.619

Gnomad OTH exome

AF:

0.609

GnomAD4 exome

AF:

0.616

AC:

900308

AN:

1461374

Hom.:

282128

Cov.:

AF XY:

0.620

AC XY:

450437

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.718

Gnomad4 ASJ exome

AF:

0.501

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:

0.517

AC:

78504

AN:

151978

Hom.:

22966

Cov.:

AF XY:

0.525

AC XY:

38956

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.616

Gnomad4 ASJ

AF:

0.508

Gnomad4 EAS

AF:

0.656

Gnomad4 SAS

AF:

0.715

Gnomad4 FIN

AF:

0.668

Gnomad4 NFE

AF:

0.620

Gnomad4 OTH

AF:

0.521

Alfa

AF:

0.592

Hom.:

49874

Bravo

AF:

0.496

TwinsUK

AF:

0.612

AC:

2269

ALSPAC

AF:

0.603

AC:

2324

ESP6500AA

AF:

0.232

AC:

1021

ESP6500EA

AF:

0.610

AC:

5242

ExAC

AF:

0.615

AC:

74673

Asia WGS

AF:

0.645

AC:

2243

AN:

3478

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

0.074

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.17

DANN

Benign

0.076

DEOGEN2

Benign

0.0033

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00054

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.0000031

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.49

.;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.38

N;.

REVEL

Benign

0.029

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.045

MPC

0.026

ClinPred

0.0010

GERP RS

2.7

Varity_R

0.069

gMVP

0.021

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