Variant 1-182056969-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001009992.1(ZNF648):c.1042T>G(p.Ser348Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000575 in 1,613,664 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

ZNF648
NM_001009992.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.631

Variant links:

Genes affected

ZNF648 (HGNC:18190): (zinc finger protein 648) 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]

ZNF648 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020365447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF648	NM_001009992.1 link	c.1042T>G	p.Ser348Ala	missense_variant	2/2	ENST00000339948.3	NP_001009992.1	Q5T619
ZNF648	XM_024453260.2 link	c.1042T>G	p.Ser348Ala	missense_variant	3/3		XP_024309028.1
ZNF648	XM_047445722.1 link	c.1042T>G	p.Ser348Ala	missense_variant	4/4		XP_047301678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF648	ENST00000339948.3 link	c.1042T>G	p.Ser348Ala	missense_variant	2/2	1	NM_001009992.1	ENSP00000344129.3		Q5T619
ZNF648	ENST00000673963.1 link	c.487T>G	p.Ser163Ala	missense_variant	2/2			ENSP00000501285.1		A0A669KBK7

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000407

AC:

100

AN:

245454

Hom.:

AF XY:

0.000467

AC XY:

AN XY:

132832

show subpopulations

Gnomad AFR exome

AF:

0.0000626

Gnomad AMR exome

AF:

0.000930

Gnomad ASJ exome

AF:

0.000303

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000561

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000594

AC:

868

AN:

1461408

Hom.:

Cov.:

AF XY:

0.000575

AC XY:

418

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000565

Gnomad4 NFE exome

AF:

0.000693

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000394

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000936

Hom.:

Bravo

AF:

0.000487

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000321

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000712

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.1042T>G (p.S348A) alteration is located in exon 2 (coding exon 1) of the ZNF648 gene. This alteration results from a T to G substitution at nucleotide position 1042, causing the serine (S) at amino acid position 348 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0021

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.3

REVEL

Benign

0.028

Sift

Benign

0.034

Sift4G

Uncertain

0.057

Polyphen

0.14

Vest4

0.12

MVP

0.18

MPC

1.1

ClinPred

0.038

GERP RS

1.6

Varity_R

0.10

gMVP

0.13

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over