chr18-74631089-A-G

Position:

• chr18-74631089-A-G

Variant summary

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

The NM_017757.3(ZNF407):​c.70A>G​(p.Thr24Ala) 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: 1.14

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=0.047002763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF407	NM_017757.3	c.70A>G	p.Thr24Ala	missense_variant	2/9	ENST00000299687.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF407	ENST00000299687.10	c.70A>G	p.Thr24Ala	missense_variant	2/9	1	NM_017757.3	P2
ZNF407	ENST00000577538.5	c.70A>G	p.Thr24Ala	missense_variant	1/7	2		A2
ZNF407	ENST00000309902.10	c.70A>G	p.Thr24Ala	missense_variant	1/4	2
ZNF407	ENST00000582337.5	c.70A>G	p.Thr24Ala	missense_variant	2/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 60

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

Dec 19, 2022

The c.70A>G (p.T24A) alteration is located in exon 1 (coding exon 1) of the ZNF407 gene. This alteration results from a A to G substitution at nucleotide position 70, causing the threonine (T) at amino acid position 24 to be replaced by an alanine (A). 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	0.070
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.83
DEOGEN2	Benign	0.020	.;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.50	.;T;T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.047	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.21	.;N;.;N
REVEL	Benign	0.045
Sift	Benign	0.12	.;T;.;T
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.038
MutPred		0.11		Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);
MVP		0.21
MPC		0.084
ClinPred		0.042	T
GERP RS		1.1
Varity_R		0.022
gMVP		0.055

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: chr18-72343045;