NM_003410.4:c.601_603delCAG

Variant names:

• chrX-24179721-CCAG-C
• NM_003410.4:c.601_603delCAG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_003410.4(ZFX):​c.601_603delCAG​(p.Gln201del) variant causes a conservative inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ZFX NM_003410.4 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21
• Publications: 0 publications found

Genes affected

ZFX (HGNC:12869): (zinc finger protein X-linked) This gene on the X chromosome is structurally similar to a related gene on the Y chromosome. It encodes a member of the krueppel C2H2-type zinc-finger protein family. The full-length protein contains an acidic transcriptional activation domain (AD), a nuclear localization sequence (NLS) and a DNA binding domain (DBD) consisting of 13 C2H2-type zinc fingers. Studies in mouse embryonic and adult hematopoietic stem cells showed that this gene was required as a transcriptional regulator for self-renewal of both stem cell types, but it was dispensable for growth and differentiation of their progeny. Multiple alternatively spliced transcript variants encoding different isoforms have been identified, but the full-length nature of some variants has not been determined. [provided by RefSeq, May 2010]

ZFX Gene-Disease associations (from GenCC):

• X-linked syndromic complex neurodevelopmental disorder

  Inheritance: XL Classification: STRONG Submitted by: ClinGen
• intellectual developmental disorder, X-linked, syndromic 37

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_003410.4. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003410.4. 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
	ZFX	NM_003410.4	MANE Select	c.601_603delCAG	p.Gln201del	conservative_inframe_deletion	Exon 5 of 10	NP_003401.2	P17010-1
	ZFX	NM_001330327.2		c.718_720delCAG	p.Gln240del	conservative_inframe_deletion	Exon 6 of 11	NP_001317256.1	P17010-3
	ZFX	NM_001178084.2		c.601_603delCAG	p.Gln201del	conservative_inframe_deletion	Exon 3 of 8	NP_001171555.1	P17010-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFX	ENST00000304543.10	TSL:5 MANE Select	c.601_603delCAG	p.Gln201del	conservative_inframe_deletion	Exon 5 of 10	ENSP00000304985.5	P17010-1
	ZFX	ENST00000379177.5	TSL:1	c.601_603delCAG	p.Gln201del	conservative_inframe_deletion	Exon 6 of 11	ENSP00000368475.1	P17010-1
	ZFX	ENST00000539115.5	TSL:1	c.-41-27601_-41-27599delCAG		intron	N/A	ENSP00000438233.1	P17010-2

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

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

hg19: chrX-24197838;