rs147229491

Positions:

• chr18-74632135-T-C

Variant summary

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

The ENST00000299687.10(ZNF407):​c.1116T>C​(p.Ala372=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,613,964 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: ZNF407 ENST00000299687.10 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.209

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=-0.86).
• BP6: Variant 18-74632135-T-C is Benign according to our data. Variant chr18-74632135-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 437359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.209 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.1116T>C	p.Ala372=	synonymous_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.1116T>C	p.Ala372=	synonymous_variant	2/9	1	NM_017757.3	ENSP00000299687	P2
ZNF407	ENST00000577538.5	c.1116T>C	p.Ala372=	synonymous_variant	1/7	2		ENSP00000463270	A2
ZNF407	ENST00000309902.10	c.1116T>C	p.Ala372=	synonymous_variant	1/4	2		ENSP00000310359
ZNF407	ENST00000582337.5	c.1116T>C	p.Ala372=	synonymous_variant	2/5	5		ENSP00000462348

Frequencies

GnomAD3 genomes AF: 0.00286 AC: 435 AN: 152160 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00985

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000759 AC: 189 AN: 249170 Hom.: 1 AF XY: 0.000577 AC XY: 78 AN XY: 135182

Gnomad AFR exome AF: 0.00904

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00239

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000324 AC: 474 AN: 1461686 Hom.: 2 Cov.: 53 AF XY: 0.000271 AC XY: 197 AN XY: 727116

Gnomad4 AFR exome AF: 0.00911

Gnomad4 AMR exome AF: 0.000648

Gnomad4 ASJ exome AF: 0.00195

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000387

Gnomad4 OTH exome AF: 0.000729

GnomAD4 genome AF: 0.00286 AC: 435 AN: 152278 Hom.: 3 Cov.: 33 AF XY: 0.00266 AC XY: 198 AN XY: 74462

Gnomad4 AFR AF: 0.00982

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00181 Hom.: 1

Bravo AF: 0.00315

Asia WGS AF: 0.000866 AC: 4 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	Labcorp Genetics (formerly Invitae), Labcorp	Jun 06, 2018	- -
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

Jan 19, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.78

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: rs147229491; hg19: chr18-72344091;