chr7-149764856-C-T

Position:

• chr7-149764856-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207336.3(ZNF467):​c.1646G>A​(p.Gly549Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF467 NM_207336.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.204

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22915089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF467	NM_207336.3	c.1646G>A	p.Gly549Glu	missense_variant	5/5	ENST00000302017.4	NP_997219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF467	ENST00000302017.4	c.1646G>A	p.Gly549Glu	missense_variant	5/5	1	NM_207336.3	ENSP00000304769.3
ZNF467	ENST00000484747.5	c.263-178G>A		intron_variant		2		ENSP00000418011.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.1646G>A (p.G549E) 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 1646, causing the glycine (G) at amino acid position 549 to be replaced by a glutamic acid (E). 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	Pathogenic	0.75
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.070
Sift	Benign	0.067	T
Sift4G	Uncertain	0.016	D
Polyphen		0.49	P
Vest4		0.19
MutPred		0.66		Loss of MoRF binding (P = 0.0312);
MVP		0.33
MPC		1.5
ClinPred		0.87	D
GERP RS		2.1
Varity_R		0.53
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-149461945; COSMIC: COSV105117056;