rs4986770

Variant names:

• chr19-51964781-G-A
• rs4986770
• NM_021632.4:c.*73C>T

Variant summary

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

The NM_021632.4(ZNF350):​c.*73C>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 0.0758 in 1,500,484 control chromosomes in the GnomAD database, including 5,551 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 0.079 (544 hom., cov: 33)
  • Exomes 𝑓: 0.076 (5007 hom.)
• Consequence: ZNF350 NM_021632.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 10 publications found

Genes affected

ZNF350 (HGNC:16656): (zinc finger protein 350) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nuclear body. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNF350-AS1 (HGNC:48598): (ZNF350 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF350	NM_021632.4	c.*73C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000243644.9	NP_067645.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF350	ENST00000243644.9	c.*73C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_021632.4	ENSP00000243644.3

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11941 AN: 152106 Hom.: 545 Cov.: 33

Gnomad AFR AF: 0.0899

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.0618

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.0894

GnomAD4 exome AF: 0.0755 AC: 101860 AN: 1348258 Hom.: 5007 Cov.: 22 AF XY: 0.0794 AC XY: 52823 AN XY: 665076

African (AFR) AF: 0.0957 AC: 2913 AN: 30454

American (AMR) AF: 0.0510 AC: 1856 AN: 36388

Ashkenazi Jewish (ASJ) AF: 0.0771 AC: 1644 AN: 21310

East Asian (EAS) AF: 0.0597 AC: 2324 AN: 38908

South Asian (SAS) AF: 0.221 AC: 16036 AN: 72614

European-Finnish (FIN) AF: 0.0584 AC: 2778 AN: 47558

Middle Eastern (MID) AF: 0.0902 AC: 479 AN: 5308

European-Non Finnish (NFE) AF: 0.0664 AC: 69052 AN: 1039774

Other (OTH) AF: 0.0854 AC: 4778 AN: 55944

GnomAD4 genome AF: 0.0785 AC: 11950 AN: 152226 Hom.: 544 Cov.: 33 AF XY: 0.0806 AC XY: 5997 AN XY: 74420

African (AFR) AF: 0.0900 AC: 3735 AN: 41520

American (AMR) AF: 0.0578 AC: 885 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3468

East Asian (EAS) AF: 0.0621 AC: 322 AN: 5186

South Asian (SAS) AF: 0.230 AC: 1105 AN: 4812

European-Finnish (FIN) AF: 0.0578 AC: 612 AN: 10594

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0686 AC: 4667 AN: 68026

Other (OTH) AF: 0.0889 AC: 188 AN: 2114

Alfa AF: 0.0726 Hom.: 573

Bravo AF: 0.0771

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.35
PhyloP100		-0.019
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: rs4986770; hg19: chr19-52468034;