18-74631194-T-C

Position:

• chr18-74631194-T-C

Variant summary

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

The NM_017757.3(ZNF407):​c.175T>C​(p.Ser59Pro) 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. 15/21 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: -0.224

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 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=0.036921352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.175T>C	p.Ser59Pro	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.175T>C	p.Ser59Pro	missense_variant	2/9	1	NM_017757.3	ENSP00000299687.4
ZNF407	ENST00000577538.5	c.175T>C	p.Ser59Pro	missense_variant	1/7	2		ENSP00000463270.1
ZNF407	ENST00000309902.10	c.175T>C	p.Ser59Pro	missense_variant	1/4	2		ENSP00000310359.5
ZNF407	ENST00000582337.5	c.175T>C	p.Ser59Pro	missense_variant	2/5	5		ENSP00000462348.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 58

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

Ambry Genetics

Mar 20, 2023

The c.175T>C (p.S59P) alteration is located in exon 1 (coding exon 1) of the ZNF407 gene. This alteration results from a T to C substitution at nucleotide position 175, causing the serine (S) at amino acid position 59 to be replaced by a proline (P). 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	0.098
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.92
DEOGEN2	Benign	0.013	.;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.15	.;T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.037	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.43	.;N;.;N
REVEL	Benign	0.018
Sift	Benign	0.072	.;T;.;T
Sift4G	Benign	0.099	T;T;T;D
Polyphen		0.0	B;B;B;B
Vest4		0.057
MutPred		0.094		Loss of phosphorylation at S59 (P = 0.0131);Loss of phosphorylation at S59 (P = 0.0131);Loss of phosphorylation at S59 (P = 0.0131);Loss of phosphorylation at S59 (P = 0.0131);
MVP		0.13
MPC		0.11
ClinPred		0.042	T
GERP RS		-5.7
Varity_R		0.083
gMVP		0.045

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: chr18-72343150;