19-43534154-T-C

Position:

• chr19-43534154-T-C

Variant summary

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

The NM_174945.3(ZNF575):​c.-86-183T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 501,728 control chromosomes in the GnomAD database, including 112,060 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 0.69 (36081 hom., cov: 33)
  • Exomes 𝑓: 0.66 (75979 hom.)
• Consequence: ZNF575 NM_174945.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364

Genes affected

ZNF575 (HGNC:27606): (zinc finger protein 575) 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF575 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF575	NM_174945.3	c.-86-183T>C		intron_variant		ENST00000314228.10	NP_777605.1
ZNF575	NM_001394237.1	c.-18+252T>C		intron_variant			NP_001381166.1
ZNF575	XM_011526793.4	c.-86-183T>C		intron_variant			XP_011525095.1
ZNF575	XM_047438637.1	c.-86-183T>C		intron_variant			XP_047294593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF575	ENST00000314228.10	c.-86-183T>C		intron_variant		2	NM_174945.3	ENSP00000315870.4

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104432 AN: 151974 Hom.: 36046 Cov.: 33

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.656 AC: 229439 AN: 349636 Hom.: 75979 Cov.: 2 AF XY: 0.655 AC XY: 119896 AN XY: 183038

Gnomad4 AFR exome AF: 0.763

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 0.596

Gnomad4 EAS exome AF: 0.745

Gnomad4 SAS exome AF: 0.645

Gnomad4 FIN exome AF: 0.690

Gnomad4 NFE exome AF: 0.640

Gnomad4 OTH exome AF: 0.666

GnomAD4 genome AF: 0.687 AC: 104513 AN: 152092 Hom.: 36081 Cov.: 33 AF XY: 0.691 AC XY: 51353 AN XY: 74336

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.688

Alfa AF: 0.649 Hom.: 33533

Bravo AF: 0.692

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs2256507; hg19: chr19-44038306;