Variant chr7-149765047-C-G 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_207336.3(ZNF467):c.1455G>C(p.Arg485Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0005 in 1,514,204 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 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

ZNF467
NM_207336.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0500

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 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=0.009029806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF467	NM_207336.3 linkuse as main transcript	c.1455G>C	p.Arg485Ser	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.1455G>C	p.Arg485Ser	missense_variant	5/5	1	NM_207336.3	ENSP00000304769.3		Q7Z7K2
ZNF467	ENST00000484747.5 linkuse as main transcript	c.263-369G>C		intron_variant		2		ENSP00000418011.1		C9JAX3

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.000131

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:

0.000471

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000319

AC:

AN:

125392

Hom.:

AF XY:

0.000399

AC XY:

AN XY:

70170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000308

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000592

Gnomad OTH exome

AF:

0.000560

GnomAD4 exome

AF:

0.000510

AC:

694

AN:

1361994

Hom.:

Cov.:

AF XY:

0.000477

AC XY:

320

AN XY:

671556

show subpopulations

Gnomad4 AFR exome

AF:

0.0000336

Gnomad4 AMR exome

AF:

0.000293

Gnomad4 ASJ exome

AF:

0.0000430

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000620

Gnomad4 OTH exome

AF:

0.000354

GnomAD4 genome

AF:

0.000414

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000472

Hom.:

Bravo

AF:

0.000604

ExAC

AF:

0.000185

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

Aug 02, 2021

The c.1455G>C (p.R485S) alteration is located in exon 5 (coding exon 4) of the ZNF467 gene. This alteration results from a G to C substitution at nucleotide position 1455, causing the arginine (R) at amino acid position 485 to be replaced by a serine (S). 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

0.91

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.43

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.0090

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.030

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.55

Vest4

0.17

MutPred

0.43

Loss of MoRF binding (P = 0.0144);

MVP

0.31

MPC

1.5

ClinPred

0.12

GERP RS

1.9

Varity_R

0.24

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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