rs558872346

Variant names:

• chr7-149764745-G-C
• rs558872346
• NM_207336.3:c.1757C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-149764745-G-C
• chr7-149764745-G-T
• chr7-149764745-G-A

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>G​(p.Pro586Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000093 in 1,548,524 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 0.000099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000092 (0 hom.)
• Consequence: ZNF467 NM_207336.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.846
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043924272).

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>G	p.Pro586Arg	missense	Exon 5 of 5	NP_997219.1	Q7Z7K2
	ZNF467	NM_001329856.2		c.263-67C>G		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.1757C>G	p.Pro586Arg	missense	Exon 5 of 5	ENSP00000304769.3	Q7Z7K2
	ZNF467	ENST00000882874.1		c.1877C>G	p.Pro626Arg	missense	Exon 5 of 5	ENSP00000552933.1
	ZNF467	ENST00000882861.1		c.1757C>G	p.Pro586Arg	missense	Exon 5 of 5	ENSP00000552920.1

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152256 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000590 AC: 11 AN: 186568 AF XY: 0.0000593

Gnomad AFR exome AF: 0.000241

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: 0.0000597

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000924 AC: 129 AN: 1396268 Hom.: 0 Cov.: 30 AF XY: 0.0000918 AC XY: 63 AN XY: 686274

African (AFR) AF: 0.0000630 AC: 2 AN: 31760

American (AMR) AF: 0.0000529 AC: 2 AN: 37818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22202

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38784

South Asian (SAS) AF: 0.000444 AC: 34 AN: 76554

European-Finnish (FIN) AF: 0.0000401 AC: 2 AN: 49840

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

European-Non Finnish (NFE) AF: 0.0000715 AC: 77 AN: 1076444

Other (OTH) AF: 0.000192 AC: 11 AN: 57400

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7 AN XY: 74396

African (AFR) AF: 0.000145 AC: 6 AN: 41476

American (AMR) AF: 0.000131 AC: 2 AN: 15292

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

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

South Asian (SAS) AF: 0.000413 AC: 2 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.0000423 AC: 5

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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	0.12
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.84
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.85
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.079
Sift	Benign	0.16	T
Sift4G	Uncertain	0.055	T
Polyphen		0.047	B
Vest4		0.11
MutPred		0.26		Loss of glycosylation at P586 (P = 0.0236)
MVP		0.13
MPC		0.51
ClinPred		0.017	T
GERP RS		2.1
Varity_R		0.019
gMVP		0.15
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: rs558872346; hg19: chr7-149461834;