X-46500596-AA-CG

Variant names:

• chrX-46500596-AA-CG
• NM_001190417.2:c.977_978delTTinsCG
• ZNF674 p.Ile326Thr

Variant summary

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

The NM_001190417.2(ZNF674):​c.977_978delTTinsCG​(p.Ile326Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF674 NM_001190417.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• Publications: 0 publications found

Genes affected

ZNF674 (HGNC:17625): (zinc finger protein 674) This gene encodes a zinc finger protein with an N-terminal Kruppel-associated box-containing (KRAB) domain and 11 Kruppel-type C2H2 zinc finger domains. Like other zinc finger proteins, this gene may function as a transcription factor. This gene resides on an area of chromosome X that has been implicated in nonsyndromic X-linked cognitive disabilities. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

ZNF674 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: XL Classification: NO_KNOWN Submitted by: Ambry Genetics
• X-linked intellectual disability

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190417.2. 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
	ZNF674	NM_001190417.2	MANE Select	c.977_978delTTinsCG	p.Ile326Thr	missense	N/A	NP_001177346.1	A0A804HHU7
	ZNF674	NM_001039891.3		c.992_993delTTinsCG	p.Ile331Thr	missense	N/A	NP_001034980.1	Q2M3X9-1
	ZNF674	NM_001146291.2		c.974_975delTTinsCG	p.Ile325Thr	missense	N/A	NP_001139763.1	Q2M3X9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF674	ENST00000683375.1	MANE Select	c.977_978delTTinsCG	p.Ile326Thr	missense	N/A	ENSP00000506769.1	A0A804HHU7
	ZNF674	ENST00000523374.5	TSL:1	c.992_993delTTinsCG	p.Ile331Thr	missense	N/A	ENSP00000429148.1	Q2M3X9-1
	ZNF674	ENST00000878263.1		c.977_978delTTinsCG	p.Ile326Thr	missense	N/A	ENSP00000548322.1

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-46360031;