19-43534154-T-C

Variant names:

• chr19-43534154-T-C
• rs2256507
• NM_174945.3:c.-86-183T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174945.3. 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
	ZNF575	NM_174945.3	MANE Select	c.-86-183T>C		intron	N/A	NP_777605.1
	ZNF575	NM_001394237.1		c.-18+252T>C		intron	N/A	NP_001381166.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF575	ENST00000314228.10	TSL:2 MANE Select	c.-86-183T>C		intron	N/A	ENSP00000315870.4
	ZNF575	ENST00000600154.1	TSL:4	n.446T>C		non_coding_transcript_exon	Exon 2 of 2
	ZNF575	ENST00000458714.2	TSL:2	c.212-183T>C		intron	N/A	ENSP00000413956.2

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

African (AFR) AF: 0.763 AC: 5882 AN: 7704

American (AMR) AF: 0.706 AC: 6638 AN: 9400

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 6776 AN: 11364

East Asian (EAS) AF: 0.745 AC: 16490 AN: 22122

South Asian (SAS) AF: 0.645 AC: 21153 AN: 32770

European-Finnish (FIN) AF: 0.690 AC: 18145 AN: 26292

Middle Eastern (MID) AF: 0.696 AC: 1579 AN: 2270

European-Non Finnish (NFE) AF: 0.640 AC: 138613 AN: 216450

Other (OTH) AF: 0.666 AC: 14163 AN: 21264

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

African (AFR) AF: 0.771 AC: 31986 AN: 41500

American (AMR) AF: 0.680 AC: 10391 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1994 AN: 3466

East Asian (EAS) AF: 0.736 AC: 3798 AN: 5162

South Asian (SAS) AF: 0.653 AC: 3156 AN: 4832

European-Finnish (FIN) AF: 0.696 AC: 7367 AN: 10588

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43618 AN: 67940

Other (OTH) AF: 0.688 AC: 1452 AN: 2110

Alfa AF: 0.654 Hom.: 50161

Bravo AF: 0.692

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.71
PhyloP100		0.36
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: rs2256507; hg19: chr19-44038306;