rs369887612

Variant names:

• chr18-75063763-C-T
• rs369887612
• NM_017757.3:c.6042C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-75063763-C-T
• chr18-75063763-C-A
• chr18-75063763-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_017757.3(ZNF407):​c.6042C>T​(p.Pro2014Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,611,208 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00059 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (25 hom.)
• Consequence: ZNF407 NM_017757.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.85
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-75063763-C-T is Benign according to our data. Variant chr18-75063763-C-T is described in ClinVar as Benign. ClinVar VariationId is 212677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.85 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00107 (1565/1458960) while in subpopulation SAS AF = 0.0169 (1458/86236). AF 95% confidence interval is 0.0162. There are 25 homozygotes in GnomAdExome4. There are 1157 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.6042C>T	p.Pro2014Pro	synonymous	Exon 9 of 9	NP_060227.2	Q9C0G0-1
	ZNF407	NM_001384475.1		c.6042C>T	p.Pro2014Pro	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.6042C>T	p.Pro2014Pro	synonymous	Exon 9 of 9	ENSP00000299687.4	Q9C0G0-1
	ZNF407	ENST00000949102.1		c.4398C>T	p.Pro1466Pro	synonymous	Exon 9 of 9	ENSP00000619161.1
	ZNF407	ENST00000949101.1		c.1452C>T	p.Pro484Pro	synonymous	Exon 9 of 9	ENSP00000619160.1

Frequencies

GnomAD3 genomes AF: 0.000598 AC: 91 AN: 152130 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00232 AC: 569 AN: 245330 AF XY: 0.00315

Gnomad AFR exome AF: 0.000198

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000135

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00107 AC: 1565 AN: 1458960 Hom.: 25 Cov.: 29 AF XY: 0.00159 AC XY: 1157 AN XY: 725892

African (AFR) AF: 0.000149 AC: 5 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39690

South Asian (SAS) AF: 0.0169 AC: 1458 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50868

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000387 AC: 43 AN: 1111774

Other (OTH) AF: 0.000878 AC: 53 AN: 60332

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152248 Hom.: 3 Cov.: 32 AF XY: 0.000927 AC XY: 69 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.000131 AC: 2 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.0176 AC: 85 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.000121

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	ZNF407-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.079
DANN	Benign	0.56
PhyloP100		-2.8
Mutation Taster		=100/0	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: rs369887612; hg19: chr18-72775719; COSMIC: COSV55256296; COSMIC: COSV55256296;