NM_174945.3:c.-86-183T>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174945.3(ZNF575):​c.-86-183T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

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>A		intron	N/A	NP_777605.1
	ZNF575	NM_001394237.1		c.-18+252T>A		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>A		intron	N/A	ENSP00000315870.4
	ZNF575	ENST00000600154.1	TSL:4	n.446T>A		non_coding_transcript_exon	Exon 2 of 2
	ZNF575	ENST00000458714.2	TSL:2	c.212-183T>A		intron	N/A	ENSP00000413956.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 350444 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 183436

African (AFR) AF: 0.00 AC: 0 AN: 7708

American (AMR) AF: 0.00 AC: 0 AN: 9418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11402

East Asian (EAS) AF: 0.00 AC: 0 AN: 22146

South Asian (SAS) AF: 0.00 AC: 0 AN: 32854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 216976

Other (OTH) AF: 0.00 AC: 0 AN: 21312

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.4
DANN	Benign	0.81
PhyloP100		0.36

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;