rs187139901

chr18-74632927-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_017757.3(ZNF407):c.1908C>T(p.Thr636=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,612,850 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (9 hom.)
• Consequence: ZNF407 NM_017757.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.807

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 18-74632927-C-T is Benign according to our data. Variant chr18-74632927-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 212659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.807 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF407	NM_017757.3	c.1908C>T	p.Thr636=	synonymous_variant	2/9	ENST00000299687.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF407	ENST00000299687.10	c.1908C>T	p.Thr636=	synonymous_variant	2/9	1	NM_017757.3	P2
ZNF407	ENST00000577538.5	c.1908C>T	p.Thr636=	synonymous_variant	1/7	2		A2
ZNF407	ENST00000309902.10	c.1908C>T	p.Thr636=	synonymous_variant	1/4	2
ZNF407	ENST00000582337.5	c.1908C>T	p.Thr636=	synonymous_variant	2/5	5

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 151946 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000629

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00397

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00378

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00242 AC: 600 AN: 248246 Hom.: 1 AF XY: 0.00236 AC XY: 318 AN XY: 134768

Gnomad AFR exome AF: 0.000389

Gnomad AMR exome AF: 0.000785

Gnomad ASJ exome AF: 0.00140

Gnomad EAS exome AF: 0.0000559

Gnomad SAS exome AF: 0.00164

Gnomad FIN exome AF: 0.00477

Gnomad NFE exome AF: 0.00342

Gnomad OTH exome AF: 0.00250

GnomAD4 exome AF: 0.00252 AC: 3676 AN: 1460786 Hom.: 9 Cov.: 43 AF XY: 0.00252 AC XY: 1829 AN XY: 726744

Gnomad4 AFR exome AF: 0.000270

Gnomad4 AMR exome AF: 0.000920

Gnomad4 ASJ exome AF: 0.00153

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00138

Gnomad4 FIN exome AF: 0.00476

Gnomad4 NFE exome AF: 0.00277

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.00241 AC: 366 AN: 152064 Hom.: 2 Cov.: 33 AF XY: 0.00203 AC XY: 151 AN XY: 74328

Gnomad4 AFR AF: 0.000627

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00397

Gnomad4 NFE AF: 0.00378

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00277 Hom.: 0

Bravo AF: 0.00186

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00234

EpiControl AF: 0.00279

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	ZNF407: BP4, BP7, BS2 -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 28, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	0.14
Dann	Benign	0.32

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: rs187139901; hg19: chr18-72344883;