16-31083850-C-T

Variant names:

• chr16-31083850-C-T
• rs11865038
• NM_014699.4:c.*758C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014699.4(ZNF646):​c.*758C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,609,334 control chromosomes in the GnomAD database, including 141,029 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 0.45 (16799 hom., cov: 33)
  • Exomes 𝑓: 0.40 (124230 hom.)
• Consequence: ZNF646 NM_014699.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 50 publications found

Genes affected

ZNF646 (HGNC:29004): (zinc finger protein 646) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PRSS53 (HGNC:34407): (serine protease 53) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255439 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014699.4. 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
	ZNF646	NM_014699.4	MANE Select	c.*758C>T		3_prime_UTR	Exon 3 of 3	NP_055514.3
	PRSS53	NM_001039503.3	MANE Select	c.1643-41G>A		intron	N/A	NP_001034592.1	Q2L4Q9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF646	ENST00000300850.5	TSL:1 MANE Select	c.*758C>T		3_prime_UTR	Exon 3 of 3	ENSP00000300850.5	O15015-2
	PRSS53	ENST00000280606.7	TSL:1 MANE Select	c.1643-41G>A		intron	N/A	ENSP00000280606.6	Q2L4Q9
	ENSG00000255439	ENST00000533518.5	TSL:1	n.*1627-41G>A		intron	N/A	ENSP00000433035.1	H0YD56

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68654 AN: 151922 Hom.: 16761 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.404

GnomAD2 exomes AF: 0.419 AC: 103847 AN: 247982 AF XY: 0.430

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.103

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.378

Gnomad OTH exome AF: 0.401

GnomAD4 exome AF: 0.399 AC: 581963 AN: 1457294 Hom.: 124230 Cov.: 34 AF XY: 0.406 AC XY: 294554 AN XY: 725046

African (AFR) AF: 0.624 AC: 20825 AN: 33392

American (AMR) AF: 0.422 AC: 18817 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8455 AN: 26086

East Asian (EAS) AF: 0.0945 AC: 3748 AN: 39670

South Asian (SAS) AF: 0.694 AC: 59808 AN: 86122

European-Finnish (FIN) AF: 0.386 AC: 20573 AN: 53314

Middle Eastern (MID) AF: 0.318 AC: 1816 AN: 5718

European-Non Finnish (NFE) AF: 0.383 AC: 424102 AN: 1108174

Other (OTH) AF: 0.396 AC: 23819 AN: 60216

GnomAD4 genome AF: 0.452 AC: 68745 AN: 152040 Hom.: 16799 Cov.: 33 AF XY: 0.454 AC XY: 33715 AN XY: 74322

African (AFR) AF: 0.618 AC: 25604 AN: 41456

American (AMR) AF: 0.423 AC: 6461 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3472

East Asian (EAS) AF: 0.106 AC: 548 AN: 5168

South Asian (SAS) AF: 0.715 AC: 3450 AN: 4828

European-Finnish (FIN) AF: 0.378 AC: 3990 AN: 10548

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26375 AN: 67976

Other (OTH) AF: 0.407 AC: 859 AN: 2108

Alfa AF: 0.410 Hom.: 21560

Bravo AF: 0.451

Asia WGS AF: 0.469 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.70
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs11865038; hg19: chr16-31095171; COSMIC: COSV54924324; COSMIC: COSV54924324;