18-74631446-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_017757.3(ZNF407):c.427G>T(p.Val143Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,613,954 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (10 hom.)
• Consequence: ZNF407 NM_017757.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.450

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002600789).
• BP6: Variant 18-74631446-G-T is Benign according to our data. Variant chr18-74631446-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 130822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF407	NM_017757.3	c.427G>T	p.Val143Phe	missense_variant	2/9	ENST00000299687.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF407	ENST00000299687.10	c.427G>T	p.Val143Phe	missense_variant	2/9	1	NM_017757.3	P2
ZNF407	ENST00000577538.5	c.427G>T	p.Val143Phe	missense_variant	1/7	2		A2
ZNF407	ENST00000309902.10	c.427G>T	p.Val143Phe	missense_variant	1/4	2
ZNF407	ENST00000582337.5	c.427G>T	p.Val143Phe	missense_variant	2/5	5

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 439 AN: 152126 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00660

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00410

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00325 AC: 810 AN: 249216 Hom.: 3 AF XY: 0.00331 AC XY: 448 AN XY: 135206

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00577

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00131

Gnomad FIN exome AF: 0.00729

Gnomad NFE exome AF: 0.00432

Gnomad OTH exome AF: 0.00331

GnomAD4 exome AF: 0.00320 AC: 4681 AN: 1461710 Hom.: 10 Cov.: 60 AF XY: 0.00318 AC XY: 2310 AN XY: 727138

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00127

Gnomad4 ASJ exome AF: 0.00597

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00154

Gnomad4 FIN exome AF: 0.00755

Gnomad4 NFE exome AF: 0.00334

Gnomad4 OTH exome AF: 0.00303

GnomAD4 genome AF: 0.00288 AC: 439 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.00292 AC XY: 217 AN XY: 74442

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00660

Gnomad4 NFE AF: 0.00410

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00371 Hom.: 5

Bravo AF: 0.00249

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000796 AC: 3

ESP6500EA AF: 0.00438 AC: 36

ExAC AF: 0.00298 AC: 360

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00414

EpiControl AF: 0.00385

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 20, 2015

- -

ZNF407-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

ZNF407: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	18
Dann	Uncertain	0.99
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.13	N
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.0026	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L;L;L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.041	D;D;T;T
Polyphen		0.0090	B;B;B;B
Vest4		0.12
MVP		0.068
MPC		0.12
ClinPred		0.0068	T
GERP RS		2.5
Varity_R		0.072
gMVP		0.12

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: rs200158544; hg19: chr18-72343402; COSMIC: COSV55270155;