chr19-51969042-A-G

Variant names:

• chr19-51969042-A-G
• rs4986773
• NM_021632.4:c.105T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021632.4(ZNF350):​c.105T>C​(p.Asp35Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,682 control chromosomes in the GnomAD database, including 81,057 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 0.39 (13331 hom., cov: 31)
  • Exomes 𝑓: 0.29 (67726 hom.)
• Consequence: ZNF350 NM_021632.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.05
• Publications: 18 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP7: Synonymous conserved (PhyloP=-6.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF350	NM_021632.4	c.105T>C	p.Asp35Asp	synonymous_variant	Exon 3 of 5	ENST00000243644.9	NP_067645.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF350	ENST00000243644.9	c.105T>C	p.Asp35Asp	synonymous_variant	Exon 3 of 5	1	NM_021632.4	ENSP00000243644.3

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58548 AN: 151852 Hom.: 13279 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.371

GnomAD2 exomes AF: 0.332 AC: 83424 AN: 251450 AF XY: 0.335

Gnomad AFR exome AF: 0.639

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.285

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.291 AC: 425528 AN: 1461710 Hom.: 67726 Cov.: 35 AF XY: 0.297 AC XY: 215865 AN XY: 727152

African (AFR) AF: 0.643 AC: 21528 AN: 33478

American (AMR) AF: 0.264 AC: 11808 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7928 AN: 26128

East Asian (EAS) AF: 0.290 AC: 11493 AN: 39688

South Asian (SAS) AF: 0.520 AC: 44886 AN: 86256

European-Finnish (FIN) AF: 0.326 AC: 17409 AN: 53412

Middle Eastern (MID) AF: 0.297 AC: 1712 AN: 5768

European-Non Finnish (NFE) AF: 0.261 AC: 289844 AN: 1111884

Other (OTH) AF: 0.313 AC: 18920 AN: 60378

GnomAD4 genome AF: 0.386 AC: 58662 AN: 151972 Hom.: 13331 Cov.: 31 AF XY: 0.391 AC XY: 29005 AN XY: 74264

African (AFR) AF: 0.632 AC: 26162 AN: 41410

American (AMR) AF: 0.294 AC: 4485 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3468

East Asian (EAS) AF: 0.286 AC: 1473 AN: 5156

South Asian (SAS) AF: 0.546 AC: 2630 AN: 4818

European-Finnish (FIN) AF: 0.343 AC: 3623 AN: 10554

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18028 AN: 67966

Other (OTH) AF: 0.376 AC: 796 AN: 2116

Alfa AF: 0.321 Hom.: 4044

Bravo AF: 0.388

Asia WGS AF: 0.494 AC: 1719 AN: 3478

EpiCase AF: 0.268

EpiControl AF: 0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.26
PhyloP100		-6.0
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4986773; hg19: chr19-52472295; COSMIC: COSV54709910; COSMIC: COSV54709910;