chr6-57134841-C-A

Variant names:

• chr6-57134841-C-A
• rs536434206
• NM_001031623.3:c.673C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001031623.3(ZNF451):​c.673C>A​(p.Gln225Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,609,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ZNF451 NM_001031623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.673C>A	p.Gln225Lys	missense	Exon 7 of 15	NP_001026794.1	Q9Y4E5-1
	ZNF451	NM_015555.3		c.673C>A	p.Gln225Lys	missense	Exon 7 of 14	NP_056370.2	Q9Y4E5-2
	ZNF451-AS1	NR_110742.1		n.235-19278G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF451	ENST00000370706.9	TSL:1 MANE Select	c.673C>A	p.Gln225Lys	missense	Exon 7 of 15	ENSP00000359740.4	Q9Y4E5-1
	ZNF451	ENST00000491832.6	TSL:1	c.673C>A	p.Gln225Lys	missense	Exon 7 of 13	ENSP00000421645.1	E9PH99
	ZNF451	ENST00000357489.7	TSL:1	c.673C>A	p.Gln225Lys	missense	Exon 7 of 14	ENSP00000350083.3	Q9Y4E5-2

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250652 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1456824 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 724986

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.0000895 AC: 4 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 86086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4880

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108748

Other (OTH) AF: 0.0000665 AC: 4 AN: 60156

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74452

African (AFR) AF: 0.0000481 AC: 2 AN: 41568

American (AMR) AF: 0.000850 AC: 13 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000219

ExAC AF: 0.00000824 AC: 1

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	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.16
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.030	D
Polyphen		0.99	D
Vest4		0.49
MutPred		0.51		Gain of methylation at Q225 (P = 0.012)
MVP		0.36
MPC		0.29
ClinPred		0.37	T
GERP RS		4.6
Varity_R		0.17
gMVP		0.56
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.22		Position offset: 29

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

Other links and lift over

dbSNP: rs536434206; hg19: chr6-56999639;