rs150419019

Positions:

• chr18-75063728-G-A

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.6007G>A​(p.Glu2003Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,612,346 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (58 hom.)
• Consequence: ZNF407 NM_017757.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 9.01

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=0.0042485595).
• BP6: Variant 18-75063728-G-A is Benign according to our data. Variant chr18-75063728-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 212676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.6007G>A	p.Glu2003Lys	missense_variant	9/9	ENST00000299687.10	NP_060227.2
ZNF407	NM_001384475.1	c.6007G>A	p.Glu2003Lys	missense_variant	9/9		NP_001371404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.6007G>A	p.Glu2003Lys	missense_variant	9/9	1	NM_017757.3	ENSP00000299687	P2
ZNF407	ENST00000579200.1	n.2447G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00578 AC: 880 AN: 152132 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00592

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00569 AC: 1400 AN: 245890 Hom.: 5 AF XY: 0.00589 AC XY: 790 AN XY: 134080

Gnomad AFR exome AF: 0.000867

Gnomad AMR exome AF: 0.00215

Gnomad ASJ exome AF: 0.000904

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000623

Gnomad FIN exome AF: 0.0287

Gnomad NFE exome AF: 0.00582

Gnomad OTH exome AF: 0.00568

GnomAD4 exome AF: 0.00596 AC: 8701 AN: 1460096 Hom.: 58 Cov.: 29 AF XY: 0.00579 AC XY: 4209 AN XY: 726340

Gnomad4 AFR exome AF: 0.000807

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.000842

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000662

Gnomad4 FIN exome AF: 0.0260

Gnomad4 NFE exome AF: 0.00618

Gnomad4 OTH exome AF: 0.00442

GnomAD4 genome AF: 0.00578 AC: 880 AN: 152250 Hom.: 7 Cov.: 32 AF XY: 0.00708 AC XY: 527 AN XY: 74426

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.00593

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00415 Hom.: 3

Bravo AF: 0.00338

TwinsUK AF: 0.00566 AC: 21

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.000713 AC: 3

ESP6500EA AF: 0.00427 AC: 36

ExAC AF: 0.00528 AC: 639

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00507

EpiControl AF: 0.00439

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	ZNF407: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 23, 2015

- -

ZNF407-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 27, 2024

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.67	P
Vest4		0.15
MVP		0.043
MPC		0.19
ClinPred		0.061	T
GERP RS		3.3
Varity_R		0.13
gMVP		0.57

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: rs150419019; hg19: chr18-72775684; COSMIC: COSV99079182; COSMIC: COSV99079182;