19-51869723-C-T

Variant names:

• chr19-51869723-C-T
• rs10411161
• NM_001370449.1:c.*2809G>A

Variant summary

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

The NM_001370449.1(ZNF577):​c.*2809G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,138 control chromosomes in the GnomAD database, including 3,923 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 0.21 (3923 hom., cov: 32)
• Consequence: ZNF577 NM_001370449.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• Publications: 35 publications found

Genes affected

ZNF577 (HGNC:28673): (zinc finger protein 577) 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 active 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF577	NM_001370449.1	c.*2809G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000638348.2	NP_001357378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF577	ENST00000638348.2	c.*2809G>A		3_prime_UTR_variant	Exon 6 of 6	2	NM_001370449.1	ENSP00000491936.2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31427 AN: 152020 Hom.: 3908 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.207 AC: 31481 AN: 152138 Hom.: 3923 Cov.: 32 AF XY: 0.214 AC XY: 15952 AN XY: 74384

African (AFR) AF: 0.314 AC: 13037 AN: 41482

American (AMR) AF: 0.230 AC: 3524 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 699 AN: 3472

East Asian (EAS) AF: 0.289 AC: 1497 AN: 5174

South Asian (SAS) AF: 0.400 AC: 1926 AN: 4816

European-Finnish (FIN) AF: 0.192 AC: 2031 AN: 10590

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8174 AN: 68000

Other (OTH) AF: 0.202 AC: 426 AN: 2110

Alfa AF: 0.150 Hom.: 5095

Bravo AF: 0.211

Asia WGS AF: 0.365 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.6
DANN	Benign	0.84
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10411161; hg19: chr19-52372976; COSMIC: COSV56814621;