chr7-149765108-T-C

Variant names:

• chr7-149765108-T-C
• rs2117386386
• NM_207336.3:c.1394A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_207336.3(ZNF467):​c.1394A>G​(p.Asp465Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000204 in 1,469,878 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ZNF467 NM_207336.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.919
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04256633).
• BP6: Variant 7-149765108-T-C is Benign according to our data. Variant chr7-149765108-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2534792.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1394A>G	p.Asp465Gly	missense	Exon 5 of 5	NP_997219.1	Q7Z7K2
	ZNF467	NM_001329856.2		c.263-430A>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.1394A>G	p.Asp465Gly	missense	Exon 5 of 5	ENSP00000304769.3	Q7Z7K2
	ZNF467	ENST00000882874.1		c.1514A>G	p.Asp505Gly	missense	Exon 5 of 5	ENSP00000552933.1
	ZNF467	ENST00000882861.1		c.1394A>G	p.Asp465Gly	missense	Exon 5 of 5	ENSP00000552920.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151930 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000242

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

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1317840 Hom.: 0 Cov.: 30 AF XY: 0.00000155 AC XY: 1 AN XY: 646388

African (AFR) AF: 0.00 AC: 0 AN: 27058

American (AMR) AF: 0.00 AC: 0 AN: 25108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21930

East Asian (EAS) AF: 0.00 AC: 0 AN: 31752

South Asian (SAS) AF: 0.00 AC: 0 AN: 72628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5050

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1046474

Other (OTH) AF: 0.00 AC: 0 AN: 54426

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.0000241 AC: 1 AN: 41516

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67918

Other (OTH) AF: 0.00 AC: 0 AN: 2108

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.091
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.57
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.99	N
PhyloP100		0.92
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	4.1	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.43		Gain of MoRF binding (P = 0.0206)
MVP		0.15
MPC		0.63
ClinPred		0.039	T
GERP RS		3.0
Varity_R		0.049
gMVP		0.27
Mutation Taster		=94/6	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: rs2117386386; hg19: chr7-149462197;