rs893186

Variant names:

• chr19-58457812-C-A
• rs893186
• NM_207395.3:c.*1233C>A

Variant summary

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

The NM_207395.3(ZNF324B):​c.*1233C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,996 control chromosomes in the GnomAD database, including 23,344 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 0.53 (23344 hom., cov: 31)
  • Exomes 𝑓: 0.71 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF324B NM_207395.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 14 publications found

Genes affected

ZNF324B (HGNC:33107): (zinc finger protein 324B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF324B	NM_207395.3	c.*1233C>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000336614.9	NP_997278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF324B	ENST00000336614.9	c.*1233C>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_207395.3	ENSP00000337473.3

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80812 AN: 151876 Hom.: 23304 Cov.: 31

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.465

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.708 AC: 17 AN: 24 Hom.: 5 Cov.: 0 AF XY: 0.700 AC XY: 14 AN XY: 20

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 7 AN: 10

Other (OTH) AF: 0.833 AC: 5 AN: 6

GnomAD4 genome AF: 0.532 AC: 80901 AN: 151996 Hom.: 23344 Cov.: 31 AF XY: 0.523 AC XY: 38868 AN XY: 74276

African (AFR) AF: 0.775 AC: 32149 AN: 41476

American (AMR) AF: 0.386 AC: 5889 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1330 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1565 AN: 5146

South Asian (SAS) AF: 0.368 AC: 1775 AN: 4820

European-Finnish (FIN) AF: 0.480 AC: 5068 AN: 10568

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31503 AN: 67940

Other (OTH) AF: 0.463 AC: 980 AN: 2116

Alfa AF: 0.470 Hom.: 12154

Bravo AF: 0.537

Asia WGS AF: 0.406 AC: 1412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.92
DANN	Benign	0.41
PhyloP100		-0.18
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: rs893186; hg19: chr19-58969179;