NM_003112.5:c.424delT

Variant names:

• chr7-21429588-AT-A
• NM_003112.5:c.424delT

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_003112.5(SP4):​c.424delT​(p.Ser142GlnfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SP4 NM_003112.5 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15
• Publications: 0 publications found

Genes affected

SP4 (HGNC:11209): (Sp4 transcription factor) The protein encoded by this gene is a transcription factor that can bind to the GC promoter region of a variety of genes, including those of the photoreceptor signal transduction system. The encoded protein binds to the same sites in promoter CpG islands as does the transcription factor SP1, although its expression is much more restricted compared to that of SP1. This gene may be involved in bipolar disorder and schizophrenia. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003112.5. 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
	SP4	NM_003112.5	MANE Select	c.424delT	p.Ser142GlnfsTer26	frameshift	Exon 3 of 6	NP_003103.2	Q02446
	SP4	NM_001326542.2		c.373delT	p.Ser125GlnfsTer26	frameshift	Exon 3 of 6	NP_001313471.1	A0A3B3IRW4
	SP4	NM_001326543.2		c.-516delT		5_prime_UTR	Exon 3 of 6	NP_001313472.1	Q32M51

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP4	ENST00000222584.8	TSL:1 MANE Select	c.424delT	p.Ser142GlnfsTer26	frameshift	Exon 3 of 6	ENSP00000222584.3	Q02446
	SP4	ENST00000959244.1		c.415delT	p.Ser139GlnfsTer26	frameshift	Exon 3 of 6	ENSP00000629303.1
	SP4	ENST00000649633.1		c.373delT	p.Ser125GlnfsTer26	frameshift	Exon 3 of 6	ENSP00000496957.1	A0A3B3IRW4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr7-21469206;