rs11865038

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-31083850-C-A
• chr16-31083850-C-T

Variant summary

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

The NM_014699.4(ZNF646):​c.*758C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,374 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF646 NM_014699.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF646	NM_014699.4	c.*758C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000300850.5	NP_055514.3
PRSS53	NM_001039503.3	c.1643-41G>T		intron_variant	Intron 10 of 10	ENST00000280606.7	NP_001034592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF646	ENST00000300850.5	c.*758C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_014699.4	ENSP00000300850.5
PRSS53	ENST00000280606.7	c.1643-41G>T		intron_variant	Intron 10 of 10	1	NM_001039503.3	ENSP00000280606.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459374 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726042

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109998

Other (OTH) AF: 0.00 AC: 0 AN: 60288

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.71
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;