1-247156608-T-G

Position:

• chr1-247156608-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001297568.2(ZNF124):​c.1014A>C​(p.Lys338Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF124 NM_001297568.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.37

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118912995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF124	NM_001297568.2	c.1014A>C	p.Lys338Asn	missense_variant	4/4	ENST00000543802.3	NP_001284497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF124	ENST00000543802.3	c.1014A>C	p.Lys338Asn	missense_variant	4/4	1	NM_001297568.2	ENSP00000440365	P1
ZNF124	ENST00000340684.10	c.828A>C	p.Lys276Asn	missense_variant	4/4	1		ENSP00000340749
ZNF124	ENST00000472531.5	c.218+2398A>C		intron_variant		2		ENSP00000462445
ZNF124	ENST00000491356.5	c.218+2398A>C		intron_variant		2		ENSP00000463191

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

The c.828A>C (p.K276N) alteration is located in exon 4 (coding exon 4) of the ZNF124 gene. This alteration results from a A to C substitution at nucleotide position 828, causing the lysine (K) at amino acid position 276 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	.;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.00015	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.7	N;.
REVEL	Benign	0.050
Sift	Uncertain	0.011	D;.
Sift4G	Uncertain	0.021	D;D
Polyphen		0.69	P;P
Vest4		0.086
MutPred		0.48		.;Loss of catalytic residue at K338 (P = 0.0016);
MVP		0.34
MPC		0.16
ClinPred		0.30	T
GERP RS		0.73
Varity_R		0.083
gMVP		0.014

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-247319910;