rs10484410

Variant names:

• chr6-57131890-T-C
• rs10484410
• NM_001031623.3:c.425-1152T>C

Variant summary

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

The NM_001031623.3(ZNF451):​c.425-1152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,242 control chromosomes in the GnomAD database, including 1,105 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 0.11 (1105 hom., cov: 32)
• Consequence: ZNF451 NM_001031623.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 11 publications found

Genes affected

ZNF451 (HGNC:21091): (zinc finger protein 451) Enables SUMO ligase activity and transcription corepressor activity. Involved in negative regulation of nitrogen compound metabolic process; negative regulation of transforming growth factor beta receptor signaling pathway; and protein sumoylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF451-AS1 (HGNC:53824): (ZNF451 regulatory antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031623.3. 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
	ZNF451	NM_001031623.3	MANE Select	c.425-1152T>C		intron	N/A	NP_001026794.1	Q9Y4E5-1
	ZNF451	NM_015555.3		c.425-1152T>C		intron	N/A	NP_056370.2	Q9Y4E5-2
	ZNF451-AS1	NR_110742.1		n.235-16327A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF451	ENST00000370706.9	TSL:1 MANE Select	c.425-1152T>C		intron	N/A	ENSP00000359740.4	Q9Y4E5-1
	ZNF451	ENST00000491832.6	TSL:1	c.425-1152T>C		intron	N/A	ENSP00000421645.1	E9PH99
	ZNF451	ENST00000357489.7	TSL:1	c.425-1152T>C		intron	N/A	ENSP00000350083.3	Q9Y4E5-2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16226 AN: 152124 Hom.: 1106 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.0964

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.0429

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.107 AC: 16222 AN: 152242 Hom.: 1105 Cov.: 32 AF XY: 0.107 AC XY: 7928 AN XY: 74416

African (AFR) AF: 0.0346 AC: 1437 AN: 41572

American (AMR) AF: 0.0961 AC: 1470 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3470

East Asian (EAS) AF: 0.0432 AC: 224 AN: 5186

South Asian (SAS) AF: 0.0452 AC: 218 AN: 4826

European-Finnish (FIN) AF: 0.180 AC: 1900 AN: 10582

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9745 AN: 67996

Other (OTH) AF: 0.126 AC: 267 AN: 2114

Alfa AF: 0.137 Hom.: 2187

Bravo AF: 0.0998

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		2.0
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: rs10484410; hg19: chr6-56996688;