chr3-44453949-T-A

Variant names:

• chr3-44453949-T-A
• rs1106499
• NM_181489.6:c.429+1172A>T

Variant summary

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

The NM_181489.6(ZNF445):​c.429+1172A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,010 control chromosomes in the GnomAD database, including 39,833 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 0.72 (39833 hom., cov: 31)
• Consequence: ZNF445 NM_181489.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 1 publications found

Genes affected

ZNF445 (HGNC:21018): (zinc finger protein 445) Enables double-stranded methylated DNA binding activity. Involved in maintenance of DNA methylation and regulation of genetic imprinting. 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF445	NM_181489.6	c.429+1172A>T		intron_variant	Intron 3 of 7	ENST00000396077.8	NP_852466.1
ZNF445	NM_001369454.1	c.429+1172A>T		intron_variant	Intron 2 of 6		NP_001356383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF445	ENST00000396077.8	c.429+1172A>T		intron_variant	Intron 3 of 7	1	NM_181489.6	ENSP00000379387.2
ZNF445	ENST00000425708.6	c.429+1172A>T		intron_variant	Intron 1 of 5	1		ENSP00000413073.2
ZNF445	ENST00000460529.1	n.597+1172A>T		intron_variant	Intron 2 of 4	1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109150 AN: 151892 Hom.: 39789 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.719 AC: 109252 AN: 152010 Hom.: 39833 Cov.: 31 AF XY: 0.723 AC XY: 53683 AN XY: 74290

African (AFR) AF: 0.723 AC: 29999 AN: 41470

American (AMR) AF: 0.802 AC: 12248 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2627 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5172 AN: 5176

South Asian (SAS) AF: 0.920 AC: 4439 AN: 4824

European-Finnish (FIN) AF: 0.621 AC: 6547 AN: 10542

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45921 AN: 67944

Other (OTH) AF: 0.732 AC: 1540 AN: 2104

Alfa AF: 0.692 Hom.: 4497

Bravo AF: 0.731

Asia WGS AF: 0.946 AC: 3291 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	2.0
DANN	Benign	0.66
PhyloP100		0.32
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: rs1106499; hg19: chr3-44495441;