Variant 1-182056480-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001009992.1(ZNF648):c.1531A>G(p.Arg511Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF648
NM_001009992.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.918

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16835108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF648	NM_001009992.1 linkuse as main transcript	c.1531A>G	p.Arg511Gly	missense_variant	2/2	ENST00000339948.3	NP_001009992.1
ZNF648	XM_024453260.2 linkuse as main transcript	c.1531A>G	p.Arg511Gly	missense_variant	3/3		XP_024309028.1
ZNF648	XM_047445722.1 linkuse as main transcript	c.1531A>G	p.Arg511Gly	missense_variant	4/4		XP_047301678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF648	ENST00000339948.3 linkuse as main transcript	c.1531A>G	p.Arg511Gly	missense_variant	2/2	1	NM_001009992.1	ENSP00000344129	P2
ZNF648	ENST00000673963.1 linkuse as main transcript	c.976A>G	p.Arg326Gly	missense_variant	2/2			ENSP00000501285	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250350

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135386

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 18, 2024

The c.1531A>G (p.R511G) alteration is located in exon 2 (coding exon 1) of the ZNF648 gene. This alteration results from a A to G substitution at nucleotide position 1531, causing the arginine (R) at amino acid position 511 to be replaced by a glycine (G). 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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.85

M_CAP

Benign

0.0033

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.85

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.060

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

0.79

Vest4

0.30

MutPred

0.56

Loss of MoRF binding (P = 0.0362);

MVP

0.095

MPC

0.51

ClinPred

0.86

GERP RS

0.36

Varity_R

0.71

gMVP

0.20

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