17-16623461-G-C

Position:

• chr17-16623461-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020787.4(ZNF624):​c.1425C>G​(p.Asn475Lys) 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: 32)
• Consequence: ZNF624 NM_020787.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.36

Genes affected

ZNF624 (HGNC:29254): (zinc finger protein 624) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046717882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF624	NM_020787.4	c.1425C>G	p.Asn475Lys	missense_variant	6/6	ENST00000311331.12	NP_065838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF624	ENST00000311331.12	c.1425C>G	p.Asn475Lys	missense_variant	6/6	2	NM_020787.4	ENSP00000310472	P1
ZNF624	ENST00000579528.1	n.1327C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Apr 09, 2024

The c.1425C>G (p.N475K) alteration is located in exon 6 (coding exon 5) of the ZNF624 gene. This alteration results from a C to G substitution at nucleotide position 1425, causing the asparagine (N) at amino acid position 475 to be replaced by a lysine (K). 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	Benign	0.23
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.58
DANN	Benign	0.86
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00027	N
LIST_S2	Benign	0.018	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.67	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.037
Sift	Benign	0.34	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.32		Gain of methylation at N475 (P = 5e-04);
MVP		0.061
MPC		0.45
ClinPred		0.060	T
GERP RS		-2.1
Varity_R		0.15
gMVP		0.029

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: chr17-16526775;