rs10484410

Positions:

• chr6-57131890-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370706.9(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 ENST00000370706.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF451	NM_001031623.3	c.425-1152T>C		intron_variant		ENST00000370706.9	NP_001026794.1
ZNF451-AS1	NR_110742.1	n.235-16327A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF451	ENST00000370706.9	c.425-1152T>C		intron_variant		1	NM_001031623.3	ENSP00000359740	P2
ZNF451-AS1	ENST00000416069.6	n.444-16327A>G		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.0961

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.0432

Gnomad4 SAS AF: 0.0452

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.126

Alfa AF: 0.141 Hom.: 1601

Bravo AF: 0.0998

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs10484410; hg19: chr6-56996688;