19-51965745-A-G

Variant names:

• chr19-51965745-A-G
• rs4988334
• NM_021632.4:c.708T>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.708T>C​(p.Cys236Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,812 control chromosomes in the GnomAD database, including 21,441 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 0.19 (3278 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18163 hom.)
• Consequence: ZNF350 NM_021632.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 19 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=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021632.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF350	NM_021632.4	MANE Select	c.708T>C	p.Cys236Cys	synonymous	Exon 5 of 5	NP_067645.3
	ZNF350-AS1	NR_103847.1		n.103-10646A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF350	ENST00000243644.9	TSL:1 MANE Select	c.708T>C	p.Cys236Cys	synonymous	Exon 5 of 5	ENSP00000243644.3	Q9GZX5
	ZNF350-AS1	ENST00000595010.5	TSL:1	n.125-10646A>G		intron	N/A
	ZNF350	ENST00000853589.1		c.777T>C	p.Cys259Cys	synonymous	Exon 6 of 6	ENSP00000523648.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29549 AN: 151868 Hom.: 3265 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.175

GnomAD2 exomes AF: 0.175 AC: 43912 AN: 251304 AF XY: 0.174

Gnomad AFR exome AF: 0.297

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.221

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.152 AC: 222041 AN: 1461826 Hom.: 18163 Cov.: 34 AF XY: 0.154 AC XY: 111844 AN XY: 727218

African (AFR) AF: 0.301 AC: 10074 AN: 33478

American (AMR) AF: 0.161 AC: 7203 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 4027 AN: 26132

East Asian (EAS) AF: 0.229 AC: 9099 AN: 39696

South Asian (SAS) AF: 0.240 AC: 20743 AN: 86258

European-Finnish (FIN) AF: 0.172 AC: 9171 AN: 53398

Middle Eastern (MID) AF: 0.141 AC: 811 AN: 5768

European-Non Finnish (NFE) AF: 0.136 AC: 151341 AN: 1111980

Other (OTH) AF: 0.158 AC: 9572 AN: 60394

GnomAD4 genome AF: 0.195 AC: 29606 AN: 151986 Hom.: 3278 Cov.: 32 AF XY: 0.198 AC XY: 14682 AN XY: 74312

African (AFR) AF: 0.300 AC: 12434 AN: 41416

American (AMR) AF: 0.159 AC: 2422 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1139 AN: 5158

South Asian (SAS) AF: 0.263 AC: 1264 AN: 4802

European-Finnish (FIN) AF: 0.185 AC: 1961 AN: 10572

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9335 AN: 67972

Other (OTH) AF: 0.177 AC: 374 AN: 2114

Alfa AF: 0.147 Hom.: 3026

Bravo AF: 0.193

Asia WGS AF: 0.276 AC: 958 AN: 3478

EpiCase AF: 0.133

EpiControl AF: 0.133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.37
PhyloP100		-1.9
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: rs4988334; hg19: chr19-52468998; COSMIC: COSV54707662; COSMIC: COSV54707662;