rs569213675

Variant names:

• chr7-149764746-G-A
• rs569213675
• NM_207336.3:c.1756C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-149764746-G-A
• chr7-149764746-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207336.3(ZNF467):​c.1756C>T​(p.Pro586Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000581 in 1,548,274 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. Variant has been reported in ClinVar as Uncertain significance (★). 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ZNF467 NM_207336.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.231
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034897655).

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.1756C>T	p.Pro586Ser	missense	Exon 5 of 5	NP_997219.1	Q7Z7K2
	ZNF467	NM_001329856.2		c.263-68C>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.1756C>T	p.Pro586Ser	missense	Exon 5 of 5	ENSP00000304769.3	Q7Z7K2
	ZNF467	ENST00000882874.1		c.1876C>T	p.Pro626Ser	missense	Exon 5 of 5	ENSP00000552933.1
	ZNF467	ENST00000882861.1		c.1756C>T	p.Pro586Ser	missense	Exon 5 of 5	ENSP00000552920.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152252 Hom.: 0 Cov.: 33

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000107 AC: 2 AN: 187702 AF XY: 0.00

Gnomad AFR exome AF: 0.0000798

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: 0.0000119

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000501 AC: 7 AN: 1396022 Hom.: 0 Cov.: 30 AF XY: 0.00000729 AC XY: 5 AN XY: 686094

African (AFR) AF: 0.0000315 AC: 1 AN: 31762

American (AMR) AF: 0.00 AC: 0 AN: 37780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22188

East Asian (EAS) AF: 0.00 AC: 0 AN: 38788

South Asian (SAS) AF: 0.00 AC: 0 AN: 76516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5466

European-Non Finnish (NFE) AF: 0.00000372 AC: 4 AN: 1076296

Other (OTH) AF: 0.0000349 AC: 2 AN: 57388

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74388

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000169 AC: 2

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	Benign	0.093
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.076
DANN	Benign	0.73
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.23
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.015
Sift	Benign	0.63	T
Sift4G	Benign	0.71	T
Polyphen		0.0010	B
Vest4		0.056
MutPred		0.28		Gain of phosphorylation at P586 (P = 0.025)
MVP		0.055
MPC		0.48
ClinPred		0.048	T
GERP RS		-3.5
Varity_R		0.021
gMVP		0.14
Mutation Taster		=98/2	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: rs569213675; hg19: chr7-149461835;