NM_017757.3:c.1908C>T

Variant names:

• chr18-74632927-C-T
• rs187139901
• NM_017757.3:c.1908C>T

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.1908C>T​(p.Thr636Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,612,850 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (9 hom.)
• Consequence: ZNF407 NM_017757.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.807
• 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

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 18-74632927-C-T is Benign according to our data. Variant chr18-74632927-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.807 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 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.1908C>T	p.Thr636Thr	synonymous	Exon 2 of 9	NP_060227.2	Q9C0G0-1
	ZNF407	NM_001384475.1		c.1908C>T	p.Thr636Thr	synonymous	Exon 2 of 9	NP_001371404.1	Q9C0G0-1
	ZNF407	NM_001146189.1		c.1908C>T	p.Thr636Thr	synonymous	Exon 1 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.1908C>T	p.Thr636Thr	synonymous	Exon 2 of 9	ENSP00000299687.4	Q9C0G0-1
	ZNF407	ENST00000577538.5	TSL:2	c.1908C>T	p.Thr636Thr	synonymous	Exon 1 of 7	ENSP00000463270.1	Q9C0G0-2
	ZNF407	ENST00000949102.1		c.1908C>T	p.Thr636Thr	synonymous	Exon 2 of 9	ENSP00000619161.1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 151946 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000629

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00397

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00378

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00242 AC: 600 AN: 248246 AF XY: 0.00236

Gnomad AFR exome AF: 0.000389

Gnomad AMR exome AF: 0.000785

Gnomad ASJ exome AF: 0.00140

Gnomad EAS exome AF: 0.0000559

Gnomad FIN exome AF: 0.00477

Gnomad NFE exome AF: 0.00342

Gnomad OTH exome AF: 0.00250

GnomAD4 exome AF: 0.00252 AC: 3676 AN: 1460786 Hom.: 9 Cov.: 43 AF XY: 0.00252 AC XY: 1829 AN XY: 726744

African (AFR) AF: 0.000270 AC: 9 AN: 33364

American (AMR) AF: 0.000920 AC: 41 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00153 AC: 40 AN: 26076

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.00138 AC: 119 AN: 86216

European-Finnish (FIN) AF: 0.00476 AC: 253 AN: 53176

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5760

European-Non Finnish (NFE) AF: 0.00277 AC: 3077 AN: 1111624

Other (OTH) AF: 0.00222 AC: 134 AN: 60316

GnomAD4 genome AF: 0.00241 AC: 366 AN: 152064 Hom.: 2 Cov.: 33 AF XY: 0.00203 AC XY: 151 AN XY: 74328

African (AFR) AF: 0.000627 AC: 26 AN: 41458

American (AMR) AF: 0.00170 AC: 26 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4806

European-Finnish (FIN) AF: 0.00397 AC: 42 AN: 10572

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

European-Non Finnish (NFE) AF: 0.00378 AC: 257 AN: 67990

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00277 Hom.: 0

Bravo AF: 0.00186

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00234

EpiControl AF: 0.00279

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	-0.49
CADD	Benign	0.14
DANN	Benign	0.32
PhyloP100		-0.81
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: rs187139901; hg19: chr18-72344883;