rs477725

Variant names:

• chr19-36883364-T-C
• rs477725
• ENST00000706165.1:c.-423-9454T>C

Variant summary

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

The ENST00000706165.1(ENSG00000291239):​c.-423-9454T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,118 control chromosomes in the GnomAD database, including 6,096 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 0.24 (6096 hom., cov: 32)
• Consequence: ENSG00000291239 ENST00000706165.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• Publications: 5 publications found

Genes affected

ENSG00000291239 (HGNC:):

ZNF345 (HGNC:16367): (zinc finger protein 345) Enables sequence-specific double-stranded 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000706165.1. 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
	ZNF345	NR_038362.2		n.169-9454T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291239	ENST00000706165.1		c.-423-9454T>C		intron	N/A	ENSP00000516244.1	C9JLX5
	ZNF345	ENST00000526123.5	TSL:3	c.46+6488T>C		intron	N/A	ENSP00000467611.1	K7EQ01
	ZNF345	ENST00000586933.5	TSL:4	c.46+6488T>C		intron	N/A	ENSP00000468757.1	K7ESK8

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36300 AN: 152000 Hom.: 6077 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.239 AC: 36359 AN: 152118 Hom.: 6096 Cov.: 32 AF XY: 0.238 AC XY: 17709 AN XY: 74364

African (AFR) AF: 0.472 AC: 19555 AN: 41446

American (AMR) AF: 0.220 AC: 3363 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1044 AN: 5178

South Asian (SAS) AF: 0.191 AC: 923 AN: 4830

European-Finnish (FIN) AF: 0.145 AC: 1538 AN: 10590

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8622 AN: 67994

Other (OTH) AF: 0.243 AC: 514 AN: 2114

Alfa AF: 0.174 Hom.: 8452

Bravo AF: 0.255

Asia WGS AF: 0.224 AC: 782 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.86
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs477725;

hg19: chr19-37374266;