chr1-247156679-C-T

Variant names:

• chr1-247156679-C-T
• rs766909729
• NM_001297568.2:c.943G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001297568.2(ZNF124):​c.943G>A​(p.Glu315Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,474 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF124 NM_001297568.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23540017).

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.943G>A	p.Glu315Lys	missense	Exon 4 of 4	NP_001284497.1	Q15973-3
	ZNF124	NM_003431.5		c.757G>A	p.Glu253Lys	missense	Exon 4 of 4	NP_003422.2
	ZNF124	NM_001297569.2		c.*465G>A		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.943G>A	p.Glu315Lys	missense	Exon 4 of 4	ENSP00000440365.2	Q15973-3
	ZNF124	ENST00000340684.10	TSL:1	c.757G>A	p.Glu253Lys	missense	Exon 4 of 4	ENSP00000340749.6	Q15973-4
	ZNF124	ENST00000915841.1		c.661G>A	p.Glu221Lys	missense	Exon 4 of 4	ENSP00000585900.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 250752 AF XY: 0.00

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

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: 0.00000137 AC: 2 AN: 1461256 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726908

African (AFR) AF: 0.0000599 AC: 2 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111814

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74374

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.6
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.084
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.032	D
Polyphen		0.99	D
Vest4		0.20
MutPred		0.43		Gain of methylation at E315 (P = 0.0045)
MVP		0.46
MPC		0.10
ClinPred		0.93	D
GERP RS		0.86
Varity_R		0.031
gMVP		0.017
Mutation Taster		=79/21	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: rs766909729; hg19: chr1-247319981;