rs2278414

Variant names:

• chr19-51964569-G-A
• rs2278414
• NM_021632.4:c.*285C>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.*285C>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 0.133 in 427,122 control chromosomes in the GnomAD database, including 4,474 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 0.12 (1314 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3160 hom.)
• Consequence: ZNF350 NM_021632.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF350	NM_021632.4	c.*285C>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.*285C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_021632.4	ENSP00000243644.3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17863 AN: 151956 Hom.: 1315 Cov.: 32

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.142 AC: 39044 AN: 275048 Hom.: 3160 Cov.: 3 AF XY: 0.146 AC XY: 20867 AN XY: 142876

African (AFR) AF: 0.0421 AC: 351 AN: 8328

American (AMR) AF: 0.139 AC: 1321 AN: 9494

Ashkenazi Jewish (ASJ) AF: 0.0970 AC: 884 AN: 9116

East Asian (EAS) AF: 0.228 AC: 4309 AN: 18934

South Asian (SAS) AF: 0.228 AC: 5213 AN: 22856

European-Finnish (FIN) AF: 0.160 AC: 2846 AN: 17738

Middle Eastern (MID) AF: 0.128 AC: 162 AN: 1268

European-Non Finnish (NFE) AF: 0.129 AC: 21994 AN: 170816

Other (OTH) AF: 0.119 AC: 1964 AN: 16498

GnomAD4 genome AF: 0.117 AC: 17868 AN: 152074 Hom.: 1314 Cov.: 32 AF XY: 0.124 AC XY: 9203 AN XY: 74336

African (AFR) AF: 0.0467 AC: 1939 AN: 41480

American (AMR) AF: 0.125 AC: 1911 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1133 AN: 5154

South Asian (SAS) AF: 0.261 AC: 1254 AN: 4802

European-Finnish (FIN) AF: 0.185 AC: 1954 AN: 10568

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8932 AN: 67986

Other (OTH) AF: 0.116 AC: 246 AN: 2116

Alfa AF: 0.128 Hom.: 1409

Bravo AF: 0.104

Asia WGS AF: 0.253 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.28
PhyloP100		-0.54
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: rs2278414; hg19: chr19-52467822;