NM_017757.3:c.4802+2708G>T

Variant names:

• chr18-74643830-G-T
• rs4243289
• NM_017757.3:c.4802+2708G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017757.3(ZNF407):​c.4802+2708G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF407 NM_017757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 3 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.4802+2708G>T		intron_variant	Intron 3 of 8	ENST00000299687.10	NP_060227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.4802+2708G>T		intron_variant	Intron 3 of 8	1	NM_017757.3	ENSP00000299687.4
ZNF407	ENST00000577538.5	c.4802+2708G>T		intron_variant	Intron 2 of 6	2		ENSP00000463270.1
ZNF407	ENST00000309902.10	c.4802+2708G>T		intron_variant	Intron 2 of 3	2		ENSP00000310359.5
ZNF407	ENST00000582337.5	c.4802+2708G>T		intron_variant	Intron 3 of 4	5		ENSP00000462348.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.20
PhyloP100		-0.44

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: rs4243289; hg19: chr18-72355786;