Variant 7-149764806-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_207336.3(ZNF467):c.1696G>A(p.Gly566Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000695 in 1,529,090 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 2 hom. )

Consequence

ZNF467
NM_207336.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.625

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012705356).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF467	NM_207336.3 linkuse as main transcript	c.1696G>A	p.Gly566Ser	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.1696G>A	p.Gly566Ser	missense_variant	5/5	1	NM_207336.3	ENSP00000304769.3		Q7Z7K2
ZNF467	ENST00000484747.5 linkuse as main transcript	c.263-128G>A		intron_variant		2		ENSP00000418011.1		C9JAX3

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000580

AC:

103

AN:

177508

Hom.:

AF XY:

0.000706

AC XY:

AN XY:

96252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000225

Gnomad ASJ exome

AF:

0.000237

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000291

Gnomad FIN exome

AF:

0.000315

Gnomad NFE exome

AF:

0.000998

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000721

AC:

993

AN:

1376738

Hom.:

Cov.:

AF XY:

0.000788

AC XY:

533

AN XY:

676550

show subpopulations

Gnomad4 AFR exome

AF:

0.0000328

Gnomad4 AMR exome

AF:

0.000255

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000763

Gnomad4 FIN exome

AF:

0.000348

Gnomad4 NFE exome

AF:

0.000820

Gnomad4 OTH exome

AF:

0.000478

GnomAD4 genome

AF:

0.000453

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000839

Hom.:

Bravo

AF:

0.000442

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000237

AC:

ESP6500EA

AF:

0.000354

AC:

ExAC

AF:

0.000576

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 10, 2021

The c.1696G>A (p.G566S) alteration is located in exon 5 (coding exon 4) of the ZNF467 gene. This alteration results from a G to A substitution at nucleotide position 1696, causing the glycine (G) at amino acid position 566 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

Benign

0.17

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.2

DANN

Benign

0.89

DEOGEN2

Benign

0.020

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.32

M_CAP

Benign

0.0075

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.2

REVEL

Benign

0.026

Sift

Benign

0.13

Sift4G

Uncertain

0.021

Polyphen

0.0020

Vest4

0.061

MVP

0.055

MPC

0.49

ClinPred

0.0096

GERP RS

1.2

Varity_R

0.053

gMVP

0.15

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