chr19-52959704-G-T

Variant names:

• chr19-52959704-G-T
• rs7507133
• NM_001202457.3:c.-16+3023C>A

Variant summary

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

The NM_001202457.3(ZNF816):​c.-16+3023C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,962 control chromosomes in the GnomAD database, including 16,278 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 0.44 (16278 hom., cov: 32)
• Consequence: ZNF816 NM_001202457.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 2 publications found

Genes affected

ZNF816 (HGNC:26995): (zinc finger protein 816) 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 by RNA polymerase II. Predicted to be integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF816-ZNF321P (HGNC:38879): (ZNF816-ZNF321P readthrough) This locus represents naturally occurring read-through transcription between the zinc finger protein 816 (ZNF816) gene and the zinc finger protein 321 (ZNF321) pseudogene on chromosome 19. The read-through transcript encodes a KRAB domain-containing protein that shares sequence identity with the upstream gene product, but it contains a distinct C-terminus encoded by exon structure from the downstream pseudogene. [provided by RefSeq, Jan 2011]

ENSG00000269082 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF816	NM_001202457.3	c.-16+3023C>A		intron_variant	Intron 1 of 3	ENST00000444460.7	NP_001189386.1
ZNF816	NM_001031665.4	c.-16+323C>A		intron_variant	Intron 2 of 4		NP_001026835.1
ZNF816	NM_001202456.3	c.-16+3013C>A		intron_variant	Intron 1 of 3		NP_001189385.1
ZNF816-ZNF321P	NM_001202473.2	c.-16+3013C>A		intron_variant	Intron 1 of 3		NP_001189402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF816	ENST00000444460.7	c.-16+3023C>A		intron_variant	Intron 1 of 3	1	NM_001202457.3	ENSP00000403266.2
ZNF816-ZNF321P	ENST00000391777.3	c.-16+3013C>A		intron_variant	Intron 1 of 3	2		ENSP00000375656.3

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66830 AN: 151846 Hom.: 16244 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.440 AC: 66921 AN: 151962 Hom.: 16278 Cov.: 32 AF XY: 0.439 AC XY: 32563 AN XY: 74260

African (AFR) AF: 0.662 AC: 27453 AN: 41440

American (AMR) AF: 0.354 AC: 5405 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1956 AN: 5156

South Asian (SAS) AF: 0.453 AC: 2181 AN: 4818

European-Finnish (FIN) AF: 0.306 AC: 3223 AN: 10546

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23657 AN: 67964

Other (OTH) AF: 0.451 AC: 950 AN: 2108

Alfa AF: 0.244 Hom.: 539

Bravo AF: 0.452

Asia WGS AF: 0.421 AC: 1468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.39
PhyloP100		0.15
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: rs7507133; hg19: chr19-53462957;