chr1-247156733-T-C

Variant names:

• chr1-247156733-T-C
• rs778126809
• NM_001297568.2:c.889A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001297568.2(ZNF124):​c.889A>G​(p.Lys297Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZNF124 NM_001297568.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89
• Publications: 0 publications found

Genes affected

ZNF124 (HGNC:12907): (zinc finger protein 124) This gene encodes a protein with an amino-terminal KRAB-A box and multiple repeated Kruppel-type (C2H2) zinc finger motifs at its carboxy terminus. The encoded protein may function as a transcription factor. Expression of this gene is increased after vascular endothelial growth factor (VEGF) stimulation in human leukemia cell lines and results in inhibition of apoptotic cell death induced by irradiation or exposure to etoposide. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2014]

ENSG00000305271 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39480618).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297568.2. 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
	ZNF124	NM_001297568.2	MANE Select	c.889A>G	p.Lys297Glu	missense	Exon 4 of 4	NP_001284497.1	Q15973-3
	ZNF124	NM_003431.5		c.703A>G	p.Lys235Glu	missense	Exon 4 of 4	NP_003422.2
	ZNF124	NM_001297569.2		c.*411A>G		3_prime_UTR	Exon 4 of 4	NP_001284498.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF124	ENST00000543802.3	TSL:1 MANE Select	c.889A>G	p.Lys297Glu	missense	Exon 4 of 4	ENSP00000440365.2	Q15973-3
	ZNF124	ENST00000340684.10	TSL:1	c.703A>G	p.Lys235Glu	missense	Exon 4 of 4	ENSP00000340749.6	Q15973-4
	ZNF124	ENST00000915841.1		c.607A>G	p.Lys203Glu	missense	Exon 4 of 4	ENSP00000585900.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00000399 AC: 1 AN: 250332 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

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: 0.00000342 AC: 5 AN: 1461026 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726796

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.0000898 AC: 4 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111744

Other (OTH) AF: 0.0000166 AC: 1 AN: 60346

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152184 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000567

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	Pathogenic	0.64
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.9
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.017	D
Polyphen		0.99	D
Vest4		0.34
MutPred		0.52		Loss of methylation at K297 (P = 0.0035)
MVP		0.46
MPC		0.41
ClinPred		0.92	D
GERP RS		0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.015
Mutation Taster		=87/13	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: rs778126809; hg19: chr1-247320035;