rs1555670651

Variant names:

• chr18-74633040-C-T
• rs1555670651
• NM_017757.3:c.2021C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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]

ZNF407 Gene-Disease associations (from GenCC):

• short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomalies

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.2021C>T	p.Ser674Phe	missense_variant	Exon 2 of 9	ENST00000299687.10	NP_060227.2

Ensembl

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

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

May 26, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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
PhyloP100		1.4
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
Mutation Taster		=93/7	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: rs1555670651; hg19: chr18-72344996; COSMIC: COSV55251253;