rs477725

Positions:

• chr19-36883364-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000526123.5(ZNF345):​c.46+6488T>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: ZNF345 ENST00000526123.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723

Genes affected

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF345	NR_038362.2	n.169-9454T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF345	ENST00000526123.5	c.46+6488T>C		intron_variant		3		ENSP00000467611
ZNF345	ENST00000586933.5	c.46+6488T>C		intron_variant		4		ENSP00000468757
ZNF345	ENST00000432005.6	n.115-9454T>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.243

Alfa AF: 0.149 Hom.: 3347

Bravo AF: 0.255

Asia WGS AF: 0.224 AC: 782 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs477725; hg19: chr19-37374266;