Genetic Variant ZNF467:p.Pro586Leu (chr7-149764745-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207336.3(ZNF467):c.1757C>T(p.Pro586Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,548,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P586A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ZNF467
NM_207336.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.846

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032298386).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207336.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF467	NM_207336.3	MANE Select	c.1757C>T	p.Pro586Leu	missense	Exon 5 of 5	NP_997219.1	Q7Z7K2
	ZNF467	NM_001329856.2		c.263-67C>T		intron	N/A	NP_001316785.1	C9JAX3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF467	ENST00000302017.4	TSL:1 MANE Select	c.1757C>T	p.Pro586Leu	missense	Exon 5 of 5	ENSP00000304769.3	Q7Z7K2
ZNF467	ENST00000882874.1		c.1877C>T	p.Pro626Leu	missense	Exon 5 of 5	ENSP00000552933.1
ZNF467	ENST00000882861.1		c.1757C>T	p.Pro586Leu	missense	Exon 5 of 5	ENSP00000552920.1

Frequencies

GnomAD3 genomes

AF:

0.0000722

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD2 exomes

AF:

0.0000536

AC:

AN:

186568

AF XY:

0.0000692

show subpopulations

Gnomad AFR exome

AF:

0.000402

Gnomad AMR exome

AF:

0.0000733

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000239

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1396268

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

686274

show subpopulations

African (AFR)

AF:

0.000283

AC:

AN:

31760

American (AMR)

AF:

0.0000793

AC:

AN:

37818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22202

East Asian (EAS)

AF:

0.00

AC:

AN:

38784

South Asian (SAS)

AF:

0.0000392

AC:

AN:

76554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5466

European-Non Finnish (NFE)

AF:

0.0000214

AC:

AN:

1076444

Other (OTH)

AF:

0.0000174

AC:

AN:

57400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.0000939

AC XY:

AN XY:

74522

show subpopulations

African (AFR)

AF:

0.000240

AC:

AN:

41598

American (AMR)

AF:

0.0000653

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000169

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0075

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.52

M_CAP

Benign

0.0095

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

PhyloP100

0.85

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.30

REVEL

Benign

0.081

Sift

Benign

0.28

Sift4G

Uncertain

0.059

Polyphen

0.020

Vest4

0.061

MutPred

0.30

Loss of disorder (P = 0.009)

MVP

0.20

MPC

0.49

ClinPred

0.017

GERP RS

2.1

Varity_R

0.022

gMVP

0.15

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over