7-149764776-C-G

Variant names:

• chr7-149764776-C-G
• rs1224395925
• NM_207336.3:c.1726G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207336.3(ZNF467):​c.1726G>C​(p.Ala576Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,371,850 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. A576T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ZNF467 NM_207336.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079338074).

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.1726G>C	p.Ala576Pro	missense	Exon 5 of 5	NP_997219.1	Q7Z7K2
	ZNF467	NM_001329856.2		c.263-98G>C		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.1726G>C	p.Ala576Pro	missense	Exon 5 of 5	ENSP00000304769.3	Q7Z7K2
	ZNF467	ENST00000882874.1		c.1846G>C	p.Ala616Pro	missense	Exon 5 of 5	ENSP00000552933.1
	ZNF467	ENST00000882861.1		c.1726G>C	p.Ala576Pro	missense	Exon 5 of 5	ENSP00000552920.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1371850 Hom.: 0 Cov.: 30 AF XY: 0.00000149 AC XY: 1 AN XY: 672726

African (AFR) AF: 0.00 AC: 0 AN: 30538

American (AMR) AF: 0.00 AC: 0 AN: 31444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20526

East Asian (EAS) AF: 0.00 AC: 0 AN: 38588

South Asian (SAS) AF: 0.0000138 AC: 1 AN: 72312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067950

Other (OTH) AF: 0.00 AC: 0 AN: 56290

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.7
DANN	Benign	0.80
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.32
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.021
Sift	Benign	0.29	T
Sift4G	Uncertain	0.016	D
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.50		Loss of helix (P = 0.0076)
MVP		0.11
MPC		0.66
ClinPred		0.047	T
GERP RS		0.56
Varity_R		0.066
gMVP		0.31
Mutation Taster		=96/4	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: rs1224395925; hg19: chr7-149461865;