rs189911859

Variant names:

• chr18-75063790-G-T
• rs189911859
• NM_017757.3:c.6069G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-75063790-G-T
• chr18-75063790-G-A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_017757.3(ZNF407):​c.6069G>T​(p.Leu2023Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 1,609,422 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: ZNF407 NM_017757.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.36
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 18-75063790-G-T is Benign according to our data. Variant chr18-75063790-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 437367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.36 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

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.6069G>T	p.Leu2023Leu	synonymous	Exon 9 of 9	NP_060227.2	Q9C0G0-1
	ZNF407	NM_001384475.1		c.6069G>T	p.Leu2023Leu	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.6069G>T	p.Leu2023Leu	synonymous	Exon 9 of 9	ENSP00000299687.4	Q9C0G0-1
	ZNF407	ENST00000949102.1		c.4425G>T	p.Leu1475Leu	synonymous	Exon 9 of 9	ENSP00000619161.1
	ZNF407	ENST00000949101.1		c.1479G>T	p.Leu493Leu	synonymous	Exon 9 of 9	ENSP00000619160.1

Frequencies

GnomAD3 genomes AF: 0.00224 AC: 340 AN: 152102 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00802

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000525 AC: 128 AN: 243790 AF XY: 0.000300

Gnomad AFR exome AF: 0.00765

Gnomad AMR exome AF: 0.000320

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000245 AC: 357 AN: 1457202 Hom.: 2 Cov.: 29 AF XY: 0.000205 AC XY: 149 AN XY: 725100

African (AFR) AF: 0.00911 AC: 305 AN: 33478

American (AMR) AF: 0.000246 AC: 11 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49142

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

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111728

Other (OTH) AF: 0.000547 AC: 33 AN: 60338

GnomAD4 genome AF: 0.00226 AC: 344 AN: 152220 Hom.: 4 Cov.: 32 AF XY: 0.00219 AC XY: 163 AN XY: 74418

African (AFR) AF: 0.00807 AC: 335 AN: 41532

American (AMR) AF: 0.000326 AC: 5 AN: 15314

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000956 Hom.: 0

Bravo AF: 0.00301

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.9
DANN	Benign	0.42
PhyloP100		1.4
Mutation Taster		=96/4	polymorphism

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: rs189911859; hg19: chr18-72775746;