NM_025040.4:c.1702A>T

Variant names:

• chr19-52015896-T-A
• rs142351310
• NM_025040.4:c.1702A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025040.4(ZNF614):​c.1702A>T​(p.Ile568Phe) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I568V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF614 NM_025040.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 5 publications found

Genes affected

ZNF614 (HGNC:24722): (zinc finger protein 614) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000297250 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05697623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF614	NM_025040.4	c.1702A>T	p.Ile568Phe	missense_variant	Exon 5 of 5	ENST00000270649.11	NP_079316.2
LOC124904755	XR_007067321.1	n.183-5355T>A		intron_variant	Intron 1 of 1
LOC124904755	XR_007067322.1	n.183-5355T>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF614	ENST00000270649.11	c.1702A>T	p.Ile568Phe	missense_variant	Exon 5 of 5	1	NM_025040.4	ENSP00000270649.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.17
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.083	T
M_CAP	Benign	0.00053	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.031
Sift	Benign	0.071	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.038
MutPred		0.28		Loss of MoRF binding (P = 0.0986);
MVP		0.13
MPC		0.20
ClinPred		0.030	T
GERP RS		-0.13
Varity_R		0.051
gMVP		0.043
Mutation Taster		=99/1	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: rs142351310; hg19: chr19-52519149;