18-74881076-C-T

Variant names:

• chr18-74881076-C-T
• rs34940122
• NM_017757.3:c.5085C>T

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. G1695G) has been classified as Likely benign.

• 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
• Publications: 0 publications found

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]

ZNF407 Gene-Disease associations (from GenCC):

• short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomalies

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017757.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF407	NM_017757.3	MANE Select	c.5085C>T	p.Gly1695Gly	synonymous	Exon 6 of 9	NP_060227.2	Q9C0G0-1
	ZNF407	NM_001384475.1		c.5085C>T	p.Gly1695Gly	synonymous	Exon 6 of 9	NP_001371404.1	Q9C0G0-1
	ZNF407	NM_001146189.1		c.5085C>T	p.Gly1695Gly	synonymous	Exon 5 of 7	NP_001139661.1	Q9C0G0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF407	ENST00000299687.10	TSL:1 MANE Select	c.5085C>T	p.Gly1695Gly	synonymous	Exon 6 of 9	ENSP00000299687.4	Q9C0G0-1
	ZNF407	ENST00000577538.5	TSL:2	c.5085C>T	p.Gly1695Gly	synonymous	Exon 5 of 7	ENSP00000463270.1	Q9C0G0-2
	ZNF407	ENST00000949102.1		c.3441C>T	p.Gly1147Gly	synonymous	Exon 6 of 9	ENSP00000619161.1

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

GnomAD2 exomes AF: 0.00526 AC: 860 AN: 163360 AF XY: 0.00430

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 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

African (AFR) AF: 0.0697 AC: 2238 AN: 32088

American (AMR) AF: 0.00371 AC: 139 AN: 37502

Ashkenazi Jewish (ASJ) AF: 0.00752 AC: 190 AN: 25276

East Asian (EAS) AF: 0.0000274 AC: 1 AN: 36554

South Asian (SAS) AF: 0.0000373 AC: 3 AN: 80464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45318

Middle Eastern (MID) AF: 0.00235 AC: 13 AN: 5534

European-Non Finnish (NFE) AF: 0.000108 AC: 117 AN: 1083950

Other (OTH) AF: 0.00515 AC: 300 AN: 58252

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

African (AFR) AF: 0.0678 AC: 2815 AN: 41520

American (AMR) AF: 0.00595 AC: 91 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 39 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67896

Other (OTH) AF: 0.0190 AC: 40 AN: 2108

Alfa AF: 0.00770 Hom.: 10

Bravo AF: 0.0222

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	6.1
DANN	Benign	0.86
PhyloP100		-0.27
Mutation Taster		=27/73	polymorphism (auto)

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

Other links and lift over

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