chr18-74881076-C-T

Position:

• chr18-74881076-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_017757.3(ZNF407):​c.5085C>T​(p.Gly1695Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 1,557,046 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.020 (101 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (107 hom.)
• Consequence: ZNF407 NM_017757.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=-0.265 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.5085C>T	p.Gly1695Gly	synonymous_variant	6/9	ENST00000299687.10	NP_060227.2
ZNF407	NM_001384475.1	c.5085C>T	p.Gly1695Gly	synonymous_variant	6/9		NP_001371404.1
ZNF407	NM_001146189.1	c.5085C>T	p.Gly1695Gly	synonymous_variant	5/7		NP_001139661.1
ZNF407	XM_017025838.3	c.5085C>T	p.Gly1695Gly	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>T	p.Gly1695Gly	synonymous_variant	6/9	1	NM_017757.3	ENSP00000299687.4
ZNF407	ENST00000577538.5	c.5085C>T	p.Gly1695Gly	synonymous_variant	5/7	2		ENSP00000463270.1
ZNF407	ENST00000581829.2	c.198C>T	p.Gly66Gly	synonymous_variant	2/4	5		ENSP00000479246.1
ZNF407	ENST00000584235.5	c.207C>T	p.Gly69Gly	synonymous_variant	2/4	3		ENSP00000481798.1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3005 AN: 151992 Hom.: 102 Cov.: 33

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0192

GnomAD3 exomes AF: 0.00526 AC: 860 AN: 163360 Hom.: 24 AF XY: 0.00430 AC XY: 378 AN XY: 87996

Gnomad AFR exome AF: 0.0786

Gnomad AMR exome AF: 0.00323

Gnomad ASJ exome AF: 0.00672

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000837

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000105

Gnomad OTH exome AF: 0.00263

GnomAD4 exome AF: 0.00214 AC: 3001 AN: 1404938 Hom.: 107 Cov.: 31 AF XY: 0.00183 AC XY: 1271 AN XY: 694500

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.00371

Gnomad4 ASJ exome AF: 0.00752

Gnomad4 EAS exome AF: 0.0000274

Gnomad4 SAS exome AF: 0.0000373

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.00515

GnomAD4 genome AF: 0.0197 AC: 3002 AN: 152108 Hom.: 101 Cov.: 33 AF XY: 0.0191 AC XY: 1419 AN XY: 74360

Gnomad4 AFR AF: 0.0678

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.0113

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0190

Alfa AF: 0.00749 Hom.: 8

Bravo AF: 0.0222

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	6.1
DANN	Benign	0.86

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: rs34940122; hg19: chr18-72593032; COSMIC: COSV55249045;