19-47557809-C-T

Variant names:

• chr19-47557809-C-T
• rs2974190
• NM_001277075.3:c.-98-1855G>A

Variant summary

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

The NM_001277075.3(ZNF541):​c.-98-1855G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,122 control chromosomes in the GnomAD database, including 9,139 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 0.23 (9139 hom., cov: 30)
• Consequence: ZNF541 NM_001277075.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680
• Publications: 6 publications found

Genes affected

ZNF541 (HGNC:25294): (zinc finger protein 541) Predicted to enable transcription corepressor activity. Predicted to be involved in histone deacetylation; negative regulation of transcription, DNA-templated; and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of histone deacetylase complex and transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNF541 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF541	NM_001277075.3	c.-98-1855G>A		intron_variant	Intron 2 of 16	ENST00000391901.8	NP_001264004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF541	ENST00000391901.8	c.-98-1855G>A		intron_variant	Intron 2 of 16	5	NM_001277075.3	ENSP00000375770.3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 34960 AN: 151002 Hom.: 9107 Cov.: 30

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.0669

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.232 AC: 35046 AN: 151122 Hom.: 9139 Cov.: 30 AF XY: 0.227 AC XY: 16721 AN XY: 73746

African (AFR) AF: 0.647 AC: 26617 AN: 41150

American (AMR) AF: 0.119 AC: 1804 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 271 AN: 3456

East Asian (EAS) AF: 0.0673 AC: 345 AN: 5130

South Asian (SAS) AF: 0.109 AC: 521 AN: 4776

European-Finnish (FIN) AF: 0.0706 AC: 729 AN: 10322

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0623 AC: 4224 AN: 67816

Other (OTH) AF: 0.179 AC: 377 AN: 2108

Alfa AF: 0.158 Hom.: 2222

Bravo AF: 0.252

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.21
PhyloP100		-0.68

Splicing

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

Other links and lift over

dbSNP: rs2974190; hg19: chr19-48061066;