rs201025365

Variant names:

• chr6-57124737-A-C
• rs201025365
• NM_001031623.3:c.190A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001031623.3(ZNF451):​c.190A>C​(p.Asn64His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000808 in 1,583,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000078 (0 hom.)
• Consequence: ZNF451 NM_001031623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050071746).

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.190A>C	p.Asn64His	missense	Exon 4 of 15	NP_001026794.1	Q9Y4E5-1
	ZNF451	NM_015555.3		c.190A>C	p.Asn64His	missense	Exon 4 of 14	NP_056370.2	Q9Y4E5-2
	ZNF451-AS1	NR_110742.1		n.235-9174T>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.190A>C	p.Asn64His	missense	Exon 4 of 15	ENSP00000359740.4	Q9Y4E5-1
	ZNF451	ENST00000491832.6	TSL:1	c.190A>C	p.Asn64His	missense	Exon 4 of 13	ENSP00000421645.1	E9PH99
	ZNF451	ENST00000357489.7	TSL:1	c.190A>C	p.Asn64His	missense	Exon 4 of 14	ENSP00000350083.3	Q9Y4E5-2

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000138 AC: 34 AN: 246422 AF XY: 0.000203

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000196

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000782 AC: 112 AN: 1431358 Hom.: 0 Cov.: 28 AF XY: 0.0000995 AC XY: 71 AN XY: 713384

African (AFR) AF: 0.00 AC: 0 AN: 32744

American (AMR) AF: 0.0000686 AC: 3 AN: 43760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25824

East Asian (EAS) AF: 0.00 AC: 0 AN: 39456

South Asian (SAS) AF: 0.000213 AC: 18 AN: 84380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5700

European-Non Finnish (NFE) AF: 0.0000672 AC: 73 AN: 1086824

Other (OTH) AF: 0.000202 AC: 12 AN: 59360

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74466

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68012

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000223 Hom.: 2

Bravo AF: 0.0000945

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000214 AC: 26

EpiCase AF: 0.000437

EpiControl AF: 0.000358

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.024
Sift	Benign	0.054	T
Sift4G	Benign	0.067	T
Polyphen		0.0040	B
Vest4		0.21
MVP		0.37
MPC		0.19
ClinPred		0.042	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.13
Mutation Taster		=96/4	polymorphism

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: rs201025365; hg19: chr6-56989535;