Variant 16-31077304-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014699.4(ZNF646):c.980A>G(p.Glu327Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,612,972 control chromosomes in the GnomAD database, including 125,382 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 0.31 ( 9906 hom., cov: 33)

Exomes 𝑓: 0.38 ( 115476 hom. )

Consequence

ZNF646
NM_014699.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.126

Variant links:

Genes affected

ZNF646 (HGNC:29004): (zinc finger protein 646) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF646 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=7.00967E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF646	NM_014699.4 linkuse as main transcript	c.980A>G	p.Glu327Gly	missense_variant	2/3	ENST00000300850.5	NP_055514.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF646	ENST00000300850.5 linkuse as main transcript	c.980A>G	p.Glu327Gly	missense_variant	2/3	1	NM_014699.4	ENSP00000300850	P2	O15015-2
ZNF646	ENST00000394979.2 linkuse as main transcript	c.980A>G	p.Glu327Gly	missense_variant	1/1			ENSP00000378429	A2	O15015-1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47383

AN:

152058

Hom.:

9905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0739

Gnomad AMI

AF:

0.441

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.499

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.382

GnomAD3 exomes

AF:

0.395

AC:

98241

AN:

248600

Hom.:

23403

AF XY:

0.386

AC XY:

51906

AN XY:

134532

show subpopulations

Gnomad AFR exome

AF:

0.0664

Gnomad AMR exome

AF:

0.456

Gnomad ASJ exome

AF:

0.488

Gnomad EAS exome

AF:

0.893

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.394

Gnomad OTH exome

AF:

0.406

GnomAD4 exome

AF:

0.380

AC:

555213

AN:

1460796

Hom.:

115476

Cov.:

AF XY:

0.376

AC XY:

273013

AN XY:

726656

show subpopulations

Gnomad4 AFR exome

AF:

0.0645

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.490

Gnomad4 EAS exome

AF:

0.903

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.390

Gnomad4 NFE exome

AF:

0.379

Gnomad4 OTH exome

AF:

0.389

GnomAD4 genome

AF:

0.311

AC:

47383

AN:

152176

Hom.:

9906

Cov.:

AF XY:

0.314

AC XY:

23364

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0738

Gnomad4 AMR

AF:

0.389

Gnomad4 ASJ

AF:

0.499

Gnomad4 EAS

AF:

0.891

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.378

Gnomad4 OTH

AF:

0.380

Alfa

AF:

0.391

Hom.:

15313

Bravo

AF:

0.314

TwinsUK

AF:

0.371

AC:

1374

ALSPAC

AF:

0.367

AC:

1416

ESP6500AA

AF:

0.0892

AC:

392

ESP6500EA

AF:

0.403

AC:

3462

ExAC

AF:

0.381

AC:

46216

Asia WGS

AF:

0.456

AC:

1589

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.018

.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

7.0e-7

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.17

N;N

REVEL

Benign

0.14

Sift

Benign

0.12

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.019

B;.

Vest4

0.097

MPC

0.39

ClinPred

0.0048

GERP RS

4.2

Varity_R

0.037

gMVP

0.63

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