rs1555670651

Positions:

• chr18-74633040-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.2021C>T​(p.Ser674Phe) 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: ZNF407 NM_017757.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

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=0.083857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.2021C>T	p.Ser674Phe	missense_variant	2/9	ENST00000299687.10	NP_060227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.2021C>T	p.Ser674Phe	missense_variant	2/9	1	NM_017757.3	ENSP00000299687	P2
ZNF407	ENST00000577538.5	c.2021C>T	p.Ser674Phe	missense_variant	1/7	2		ENSP00000463270	A2
ZNF407	ENST00000309902.10	c.2021C>T	p.Ser674Phe	missense_variant	1/4	2		ENSP00000310359
ZNF407	ENST00000582337.5	c.2021C>T	p.Ser674Phe	missense_variant	2/5	5		ENSP00000462348

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 43

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

Genetic Services Laboratory, University of Chicago

May 26, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	.;.;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.62	.;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.084	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M;M;M
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	.;N;.;N
REVEL	Benign	0.088
Sift	Uncertain	0.0070	.;D;.;T
Sift4G	Benign	0.076	T;T;T;T
Polyphen		0.85	P;P;P;P
Vest4		0.21
MutPred		0.20		Loss of phosphorylation at S674 (P = 0.0061);Loss of phosphorylation at S674 (P = 0.0061);Loss of phosphorylation at S674 (P = 0.0061);Loss of phosphorylation at S674 (P = 0.0061);
MVP		0.10
MPC		0.23
ClinPred		0.42	T
GERP RS		4.0
Varity_R		0.051
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs1555670651; hg19: chr18-72344996; COSMIC: COSV55251253;