rs6786

Positions:

• chr12-6666801-A-G
• chr12-6666801-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001385745.1(ZNF384):​c.*913T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 170,308 control chromosomes in the GnomAD database, including 36,289 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (33442 hom., cov: 30)
  • Exomes 𝑓: 0.48 (2847 hom.)
• Consequence: ZNF384 NM_001385745.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF384	NM_001385745.1	c.*913T>C		3_prime_UTR_variant	12/12	ENST00000683879.1	NP_001372674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF384	ENST00000683879.1	c.*913T>C		3_prime_UTR_variant	12/12		NM_001385745.1	ENSP00000507462	P4
	ENST00000586338.2	n.134-722A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.641 AC: 95919 AN: 149638 Hom.: 33397 Cov.: 30

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.445

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.483 AC: 9962 AN: 20604 Hom.: 2847 Cov.: 0 AF XY: 0.480 AC XY: 4570 AN XY: 9522

Gnomad4 AFR exome AF: 0.895

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.406

Gnomad4 EAS exome AF: 0.0747

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.581

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.641 AC: 96005 AN: 149704 Hom.: 33442 Cov.: 30 AF XY: 0.628 AC XY: 45905 AN XY: 73074

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.575

Alfa AF: 0.570 Hom.: 3918

Bravo AF: 0.648

Asia WGS AF: 0.396 AC: 1363 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs6786; hg19: chr12-6775967;