chr9-96417727-C-G

Variant names:

• chr9-96417727-C-G
• rs1288451675
• NM_153695.4:c.306G>C

Variant summary

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

The NM_153695.4(ZNF367):​c.306G>C​(p.Glu102Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000932 in 1,072,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. E102K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: ZNF367 NM_153695.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.874
• Publications: 0 publications found

Genes affected

ZNF367 (HGNC:18320): (zinc finger protein 367) Enables DNA-binding transcription factor activity. Acts upstream of or within regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12601936).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153695.4. 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
	ZNF367	NM_153695.4	MANE Select	c.306G>C	p.Glu102Asp	missense	Exon 1 of 5	NP_710162.1	Q7RTV3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF367	ENST00000375256.5	TSL:1 MANE Select	c.306G>C	p.Glu102Asp	missense	Exon 1 of 5	ENSP00000364405.4	Q7RTV3-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.32e-7 AC: 1 AN: 1072468 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 507080

African (AFR) AF: 0.00 AC: 0 AN: 22588

American (AMR) AF: 0.00 AC: 0 AN: 8200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14036

East Asian (EAS) AF: 0.00 AC: 0 AN: 26204

South Asian (SAS) AF: 0.0000510 AC: 1 AN: 19618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2892

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 913902

Other (OTH) AF: 0.00 AC: 0 AN: 43134

GnomAD4 genome Cov.: 33

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	0.25
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.66	N
PhyloP100		0.87
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.019
Sift	Benign	0.084	T
Sift4G	Benign	0.61	T
Polyphen		0.016	B
Vest4		0.075
MutPred		0.24		Gain of loop (P = 0.0121)
MVP		0.068
MPC		1.0
ClinPred		0.086	T
GERP RS		2.4
Varity_R		0.047
gMVP		0.18
Mutation Taster		=85/15	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: rs1288451675; hg19: chr9-99180009;