rs754942254

Variant names:

• chr18-75063439-G-A
• rs754942254
• NM_017757.3:c.5718G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_017757.3(ZNF407):​c.5718G>A​(p.Thr1906Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000758 in 1,608,962 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: ZNF407 NM_017757.3 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.55
• 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

ENSG00000278607 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-4.55 with no splicing effect.

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.5718G>A	p.Thr1906Thr	synonymous	Exon 9 of 9	NP_060227.2	Q9C0G0-1
	ZNF407	NM_001384475.1		c.5718G>A	p.Thr1906Thr	synonymous	Exon 9 of 9	NP_001371404.1	Q9C0G0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF407	ENST00000299687.10	TSL:1 MANE Select	c.5718G>A	p.Thr1906Thr	synonymous	Exon 9 of 9	ENSP00000299687.4	Q9C0G0-1
	ZNF407	ENST00000949102.1		c.4074G>A	p.Thr1358Thr	synonymous	Exon 9 of 9	ENSP00000619161.1
	ZNF407	ENST00000949101.1		c.1128G>A	p.Thr376Thr	synonymous	Exon 9 of 9	ENSP00000619160.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000726 AC: 17 AN: 234192 AF XY: 0.0000701

Gnomad AFR exome AF: 0.0000722

Gnomad AMR exome AF: 0.000268

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000504

Gnomad NFE exome AF: 0.0000479

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.0000769 AC: 112 AN: 1456812 Hom.: 0 Cov.: 29 AF XY: 0.0000814 AC XY: 59 AN XY: 724508

African (AFR) AF: 0.0000898 AC: 3 AN: 33404

American (AMR) AF: 0.000408 AC: 18 AN: 44148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85724

European-Finnish (FIN) AF: 0.0000387 AC: 2 AN: 51684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000729 AC: 81 AN: 1110450

Other (OTH) AF: 0.0000998 AC: 6 AN: 60132

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74312

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.000196 AC: 3 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000848 Hom.: 0

Bravo AF: 0.0000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.33
DANN	Benign	0.72
PhyloP100		-4.6

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: rs754942254; hg19: chr18-72775395;