Variant chr7-149764824-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_207336.3(ZNF467):c.1678C>T(p.Arg560Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000865 in 1,387,368 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: 𝑓 0.0 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF467
NM_207336.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

ZNF467 (HGNC:23154): (zinc finger protein 467) The protein encoded by this gene is a zinc finger protein whose function has not yet been elucidated in humans. However, the mouse ortholog of this protein enhances adipocyte differentiation and suppresses osteoblast differentiation in bone marrow. The mouse protein also is a transcription factor for several genes and can help recruit histone deacetylase complexes. [provided by RefSeq, Aug 2016]

ZNF467 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26614147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF467	NM_207336.3 linkuse as main transcript	c.1678C>T	p.Arg560Trp	missense_variant	5/5	ENST00000302017.4	NP_997219.1	Q7Z7K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF467	ENST00000302017.4 linkuse as main transcript	c.1678C>T	p.Arg560Trp	missense_variant	5/5	1	NM_207336.3	ENSP00000304769.3		Q7Z7K2
ZNF467	ENST00000484747.5 linkuse as main transcript	c.263-146C>T		intron_variant		2		ENSP00000418011.1		C9JAX3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152258

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000475

AC:

AN:

189576

Hom.:

AF XY:

0.0000484

AC XY:

AN XY:

103262

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000383

Gnomad SAS exome

AF:

0.0000498

Gnomad FIN exome

AF:

0.0000622

Gnomad NFE exome

AF:

0.0000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000865

AC:

AN:

1387368

Hom.:

Cov.:

AF XY:

0.00000439

AC XY:

AN XY:

683056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000129

Gnomad4 SAS exome

AF:

0.0000132

Gnomad4 FIN exome

AF:

0.0000204

Gnomad4 NFE exome

AF:

0.00000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74388

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000582

AC:

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

Jun 27, 2023

The c.1678C>T (p.R560W) alteration is located in exon 5 (coding exon 4) of the ZNF467 gene. This alteration results from a C to T substitution at nucleotide position 1678, causing the arginine (R) at amino acid position 560 to be replaced by a tryptophan (W). 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

0.93

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

0.068

Eigen_PC

Benign

0.0020

FATHMM_MKL

Benign

0.30

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.1

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.18

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.45

MutPred

0.38

Loss of disorder (P = 0.0073);

MVP

0.49

MPC

1.4

ClinPred

0.50

GERP RS

4.0

Varity_R

0.38

gMVP

0.56

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