chr12-6672502-G-C

Position:

• chr12-6672502-G-C

Variant summary

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

The NM_001385745.1(ZNF384):​c.1035C>G​(p.Ile345Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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. I345T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF384 NM_001385745.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

Genes affected

ZNF384 (HGNC:11955): (zinc finger protein 384) This gene encodes a C2H2-type zinc finger protein, which may function as a transcription factor. This gene also contains long CAG trinucleotide repeats that encode consecutive glutamine residues. The protein appears to bind and regulate the promoters of the extracellular matrix genes MMP1, MMP3, MMP7 and COL1A1. Studies in mouse suggest that nuclear matrix transcription factors (NP/NMP4) may be part of a general mechanical pathway that couples cell construction and function during extracellular matrix remodeling. Alternative splicing results in multiple transcript variants. Recurrent rearrangements of this gene with the Ewing's sarcoma gene, EWSR1 on chromosome 22, or with the TAF15 gene on chromosome 17, or with the TCF3 (E2A) gene on chromosome 19, have been observed in acute leukemia. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Apr 2011]

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=0.18266252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF384	NM_001385745.1	c.1035C>G	p.Ile345Met	missense_variant	9/12	ENST00000683879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF384	ENST00000683879.1	c.1035C>G	p.Ile345Met	missense_variant	9/12		NM_001385745.1	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T;T;T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.99	L;L;.
MutationTaster	Benign	0.74	D;D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.38	N;N;.
REVEL	Benign	0.22
Sift	Benign	0.098	T;T;.
Sift4G	Benign	0.21	T;T;.
Polyphen		0.090	B;B;.
Vest4		0.40
MutPred		0.24		Gain of catalytic residue at K318 (P = 0.0054);Gain of catalytic residue at K318 (P = 0.0054);.;
MVP		0.36
MPC		0.61
ClinPred		0.33	T
GERP RS		5.3
Varity_R		0.10
gMVP		0.17

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: chr12-6781668;