rs34940122

Positions:

• chr18-74881076-C-G
• chr18-74881076-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_017757.3(ZNF407):​c.5085C>G​(p.Gly1695=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 1,556,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: ZNF407 NM_017757.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.265

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 18-74881076-C-G is Benign according to our data. Variant chr18-74881076-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 212672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.265 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.5085C>G	p.Gly1695=	synonymous_variant	6/9	ENST00000299687.10	NP_060227.2
ZNF407	NM_001384475.1	c.5085C>G	p.Gly1695=	synonymous_variant	6/9		NP_001371404.1
ZNF407	NM_001146189.1	c.5085C>G	p.Gly1695=	synonymous_variant	5/7		NP_001139661.1
ZNF407	XM_017025838.3	c.5085C>G	p.Gly1695=	synonymous_variant	6/8		XP_016881327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.5085C>G	p.Gly1695=	synonymous_variant	6/9	1	NM_017757.3	ENSP00000299687	P2
ZNF407	ENST00000577538.5	c.5085C>G	p.Gly1695=	synonymous_variant	5/7	2		ENSP00000463270	A2
ZNF407	ENST00000581829.2	c.201C>G	p.Gly67=	synonymous_variant	2/4	5		ENSP00000479246
ZNF407	ENST00000584235.5	c.207C>G	p.Gly69=	synonymous_variant	2/4	3		ENSP00000481798

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152014 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000300 AC: 49 AN: 163360 Hom.: 0 AF XY: 0.000261 AC XY: 23 AN XY: 87996

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000347

Gnomad EAS exome AF: 0.000242

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00225

Gnomad NFE exome AF: 0.000240

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000235 AC: 33 AN: 1404900 Hom.: 0 Cov.: 31 AF XY: 0.0000274 AC XY: 19 AN XY: 694472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000119

Gnomad4 EAS exome AF: 0.0000274

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000331

Gnomad4 NFE exome AF: 0.0000120

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152014 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74248

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 23, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	2.3
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34940122; hg19: chr18-72593032;