chr19-58255802-T-C

Variant names:

• chr19-58255802-T-C
• rs260454
• NM_014480.4:c.245-5049T>C

Variant summary

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

The NM_001387410.1(ZNF544):​c.407-5049T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,100 control chromosomes in the GnomAD database, including 27,452 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 0.60 (27452 hom., cov: 33)
• Consequence: ZNF544 NM_001387410.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 11 publications found

Genes affected

ZNF544 (HGNC:16759): (zinc finger protein 544) Predicted to enable DNA-binding transcription activator 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000283515 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387410.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF544	NM_014480.4	MANE Select	c.245-5049T>C		intron	N/A	NP_055295.2
	ZNF544	NM_001387410.1		c.407-5049T>C		intron	N/A	NP_001374339.1
	ZNF544	NM_001387413.1		c.407-5049T>C		intron	N/A	NP_001374342.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF544	ENST00000687789.1	MANE Select	c.245-5049T>C		intron	N/A	ENSP00000510489.1
	ZNF544	ENST00000269829.5	TSL:1	c.245-5049T>C		intron	N/A	ENSP00000269829.4
	ZNF544	ENST00000596652.5	TSL:1	c.245-5049T>C		intron	N/A	ENSP00000469635.1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90806 AN: 151982 Hom.: 27416 Cov.: 33

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.598 AC: 90889 AN: 152100 Hom.: 27452 Cov.: 33 AF XY: 0.600 AC XY: 44574 AN XY: 74344

African (AFR) AF: 0.678 AC: 28137 AN: 41478

American (AMR) AF: 0.634 AC: 9689 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2332 AN: 3472

East Asian (EAS) AF: 0.602 AC: 3111 AN: 5170

South Asian (SAS) AF: 0.504 AC: 2428 AN: 4818

European-Finnish (FIN) AF: 0.582 AC: 6160 AN: 10580

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.544 AC: 36999 AN: 67974

Other (OTH) AF: 0.601 AC: 1272 AN: 2116

Alfa AF: 0.585 Hom.: 8858

Bravo AF: 0.606

Asia WGS AF: 0.541 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.4
DANN	Benign	0.54
PhyloP100		-1.5
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: rs260454; hg19: chr19-58767168;