7-149765129-G-A

Variant names:

• chr7-149765129-G-A
• rs773158806
• NM_207336.3:c.1373C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207336.3(ZNF467):​c.1373C>T​(p.Pro458Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000405 in 1,480,646 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: ZNF467 NM_207336.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.30
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1373C>T	p.Pro458Leu	missense	Exon 5 of 5	NP_997219.1	Q7Z7K2
	ZNF467	NM_001329856.2		c.263-451C>T		intron	N/A	NP_001316785.1	C9JAX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF467	ENST00000302017.4	TSL:1 MANE Select	c.1373C>T	p.Pro458Leu	missense	Exon 5 of 5	ENSP00000304769.3	Q7Z7K2
	ZNF467	ENST00000882874.1		c.1493C>T	p.Pro498Leu	missense	Exon 5 of 5	ENSP00000552933.1
	ZNF467	ENST00000882861.1		c.1373C>T	p.Pro458Leu	missense	Exon 5 of 5	ENSP00000552920.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151968 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

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

GnomAD2 exomes AF: 0.0000106 AC: 1 AN: 94738 AF XY: 0.0000186

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000376 AC: 5 AN: 1328678 Hom.: 0 Cov.: 30 AF XY: 0.00000459 AC XY: 3 AN XY: 653342

African (AFR) AF: 0.00 AC: 0 AN: 27238

American (AMR) AF: 0.00 AC: 0 AN: 26946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22754

East Asian (EAS) AF: 0.00 AC: 0 AN: 31570

South Asian (SAS) AF: 0.0000671 AC: 5 AN: 74520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4992

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1052242

Other (OTH) AF: 0.00 AC: 0 AN: 54808

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151968 Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1 AN XY: 74252

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67936

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000109 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.3
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-8.2	D
REVEL	Benign	0.27
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.51
MutPred		0.38		Gain of MoRF binding (P = 0.0648)
MVP		0.53
MPC		1.4
ClinPred		0.97	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.42
gMVP		0.29
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs773158806; hg19: chr7-149462218;