rs750218080

Variant names:

• chr18-74634921-C-G
• rs750218080
• NM_017757.3:c.3902C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-74634921-C-G
• chr18-74634921-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017757.3(ZNF407):​c.3902C>G​(p.Pro1301Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1301L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF407 NM_017757.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19260058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.3902C>G	p.Pro1301Arg	missense_variant	Exon 2 of 9	ENST00000299687.10	NP_060227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.3902C>G	p.Pro1301Arg	missense_variant	Exon 2 of 9	1	NM_017757.3	ENSP00000299687.4
ZNF407	ENST00000577538.5	c.3902C>G	p.Pro1301Arg	missense_variant	Exon 1 of 7	2		ENSP00000463270.1
ZNF407	ENST00000309902.10	c.3902C>G	p.Pro1301Arg	missense_variant	Exon 1 of 4	2		ENSP00000310359.5
ZNF407	ENST00000582337.5	c.3902C>G	p.Pro1301Arg	missense_variant	Exon 2 of 5	5		ENSP00000462348.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461566 Hom.: 0 Cov.: 41 AF XY: 0.00000275 AC XY: 2 AN XY: 727050

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111824

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	.;.;.;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.72	.;T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.2	M;M;M;M
PhyloP100		3.1
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	.;N;.;N
REVEL	Benign	0.28
Sift	Uncertain	0.0010	.;D;.;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.98	D;D;D;P
Vest4		0.16
MutPred		0.40		Gain of ubiquitination at K1306 (P = 0.0662);Gain of ubiquitination at K1306 (P = 0.0662);Gain of ubiquitination at K1306 (P = 0.0662);Gain of ubiquitination at K1306 (P = 0.0662);
MVP		0.18
MPC		0.21
ClinPred		0.79	D
GERP RS		5.7
Varity_R		0.086
gMVP		0.25

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: rs750218080; hg19: chr18-72346877;