19-51965039-A-G

Position:

• chr19-51965039-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_021632.4(ZNF350):​c.1414T>C​(p.Ser472Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,614,098 control chromosomes in the GnomAD database, including 1,191 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.027 (69 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1122 hom.)
• Consequence: ZNF350 NM_021632.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021763444).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0267 (4063/152230) while in subpopulation NFE AF= 0.0377 (2565/68024). AF 95% confidence interval is 0.0365. There are 69 homozygotes in gnomad4. There are 2014 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF350	NM_021632.4	c.1414T>C	p.Ser472Pro	missense_variant	5/5	ENST00000243644.9
ZNF350-AS1	NR_103847.1	n.103-11352A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF350	ENST00000243644.9	c.1414T>C	p.Ser472Pro	missense_variant	5/5	1	NM_021632.4	P1
ZNF350-AS1	ENST00000595010.4	n.121-11352A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0267 AC: 4063 AN: 152112 Hom.: 69 Cov.: 32

Gnomad AFR AF: 0.00705

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0344

GnomAD3 exomes AF: 0.0305 AC: 7670 AN: 251214 Hom.: 156 AF XY: 0.0324 AC XY: 4401 AN XY: 135752

Gnomad AFR exome AF: 0.00800

Gnomad AMR exome AF: 0.0209

Gnomad ASJ exome AF: 0.0268

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0396

Gnomad FIN exome AF: 0.0361

Gnomad NFE exome AF: 0.0385

Gnomad OTH exome AF: 0.0297

GnomAD4 exome AF: 0.0360 AC: 52591 AN: 1461868 Hom.: 1122 Cov.: 34 AF XY: 0.0364 AC XY: 26452 AN XY: 727236

Gnomad4 AFR exome AF: 0.00585

Gnomad4 AMR exome AF: 0.0206

Gnomad4 ASJ exome AF: 0.0255

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0376

Gnomad4 FIN exome AF: 0.0360

Gnomad4 NFE exome AF: 0.0391

Gnomad4 OTH exome AF: 0.0317

GnomAD4 genome AF: 0.0267 AC: 4063 AN: 152230 Hom.: 69 Cov.: 32 AF XY: 0.0271 AC XY: 2014 AN XY: 74424

Gnomad4 AFR AF: 0.00703

Gnomad4 AMR AF: 0.0297

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0313

Gnomad4 FIN AF: 0.0327

Gnomad4 NFE AF: 0.0377

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0346 Hom.: 181

Bravo AF: 0.0261

TwinsUK AF: 0.0345 AC: 128

ALSPAC AF: 0.0381 AC: 147

ESP6500AA AF: 0.00817 AC: 36

ESP6500EA AF: 0.0385 AC: 331

ExAC AF: 0.0307 AC: 3733

Asia WGS AF: 0.0140 AC: 50 AN: 3478

EpiCase AF: 0.0376

EpiControl AF: 0.0388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.9
DANN	Benign	0.92
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.026
Sift	Benign	0.30	T
Sift4G	Benign	0.27	T
Polyphen		0.0090	B
Vest4		0.033
MPC		0.25
ClinPred		0.0017	T
GERP RS		-3.1
Varity_R		0.15
gMVP		0.057

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

Publications

LitVar

Other links and lift over

dbSNP: rs4986771; hg19: chr19-52468292;