rs797046128

Positions:

• chr18-74635681-C-A
• chr18-74635681-C-T

Variant summary

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

The NM_017757.3(ZNF407):​c.4662C>A​(p.Phe1554Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F1554F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF407 NM_017757.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

Genes affected

ZNF407 (HGNC:19904): (zinc finger protein 407) This gene encodes a zinc finger protein whose exact function is not known. It may be involved in transcriptional regulation. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

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=0.16768038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF407	NM_017757.3	c.4662C>A	p.Phe1554Leu	missense_variant	2/9	ENST00000299687.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF407	ENST00000299687.10	c.4662C>A	p.Phe1554Leu	missense_variant	2/9	1	NM_017757.3	P2
ZNF407	ENST00000577538.5	c.4662C>A	p.Phe1554Leu	missense_variant	1/7	2		A2
ZNF407	ENST00000309902.10	c.4662C>A	p.Phe1554Leu	missense_variant	1/4	2
ZNF407	ENST00000582337.5	c.4662C>A	p.Phe1554Leu	missense_variant	2/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	.;.;.;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.80	.;T;T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-1.6	N;N;N;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.1	.;N;.;N
REVEL	Benign	0.18
Sift	Benign	0.23	.;T;.;T
Sift4G	Uncertain	0.050	T;T;T;T
Polyphen		0.99	D;D;P;P
Vest4		0.63
MutPred		0.63		Gain of MoRF binding (P = 0.1331);Gain of MoRF binding (P = 0.1331);Gain of MoRF binding (P = 0.1331);Gain of MoRF binding (P = 0.1331);
MVP		0.20
MPC		0.50
ClinPred		0.83	D
GERP RS		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.068
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs797046128; hg19: chr18-72347637;