chr19-58471017-A-G

Variant names:

• chr19-58471017-A-G
• rs10418774
• NM_014347.3:c.525A>G

Variant summary

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

The NM_014347.3(ZNF324):​c.525A>G​(p.Arg175Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,614,140 control chromosomes in the GnomAD database, including 806,942 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 1.0 (76163 hom., cov: 34)
  • Exomes 𝑓: 1.0 (730779 hom.)
• Consequence: ZNF324 NM_014347.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 13 publications found

Genes affected

ZNF324 (HGNC:14096): (zinc finger protein 324) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Acts upstream of or within with a positive effect on G1/S transition of mitotic cell cycle and cell population proliferation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-2.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014347.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF324	NM_014347.3	MANE Select	c.525A>G	p.Arg175Arg	synonymous	Exon 4 of 4	NP_055162.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF324	ENST00000196482.4	TSL:1 MANE Select	c.525A>G	p.Arg175Arg	synonymous	Exon 4 of 4	ENSP00000196482.3
	ZNF324	ENST00000536459.6	TSL:2	c.525A>G	p.Arg175Arg	synonymous	Exon 4 of 4	ENSP00000444812.1
	ZNF324	ENST00000593925.1	TSL:2	c.99A>G	p.Arg33Arg	synonymous	Exon 1 of 2	ENSP00000471778.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152219 AN: 152230 Hom.: 76104 Cov.: 34

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.998

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD2 exomes AF: 1.00 AC: 251167 AN: 251200 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.998

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 1.00 AC: 1461675 AN: 1461792 Hom.: 730779 Cov.: 111 AF XY: 1.00 AC XY: 727137 AN XY: 727196

African (AFR) AF: 1.00 AC: 33480 AN: 33480

American (AMR) AF: 1.00 AC: 44724 AN: 44724

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26134 AN: 26134

East Asian (EAS) AF: 0.997 AC: 39587 AN: 39700

South Asian (SAS) AF: 1.00 AC: 86256 AN: 86256

European-Finnish (FIN) AF: 1.00 AC: 53326 AN: 53326

Middle Eastern (MID) AF: 1.00 AC: 5768 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1112009 AN: 1112010

Other (OTH) AF: 1.00 AC: 60391 AN: 60394

GnomAD4 genome AF: 1.00 AC: 152337 AN: 152348 Hom.: 76163 Cov.: 34 AF XY: 1.00 AC XY: 74478 AN XY: 74486

African (AFR) AF: 1.00 AC: 41590 AN: 41590

American (AMR) AF: 1.00 AC: 15310 AN: 15310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5158 AN: 5168

South Asian (SAS) AF: 1.00 AC: 4833 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68034 AN: 68034

Other (OTH) AF: 1.00 AC: 2116 AN: 2116

Alfa AF: 1.00 Hom.: 22292

Bravo AF: 1.00

Asia WGS AF: 0.999 AC: 3476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.48
PhyloP100		-2.3
PromoterAI		-0.00080	Neutral
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: rs10418774; hg19: chr19-58982384; COSMIC: COSV52181265; COSMIC: COSV52181265;