NM_018013.4:c.2250_2252dupGCC

Variant names:

• chr6-107635074-CA-CAGC
• NM_018013.4:c.2232_2233dupGC

Variant summary

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

The NM_018013.4(SOBP):​c.2232_2233dupGC​(p.Pro745ArgfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SOBP NM_018013.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• Publications: 0 publications found

Genes affected

SOBP (HGNC:29256): (sine oculis binding protein homolog) The protein encoded by this gene is a nuclear zinc finger protein that is involved in development of the cochlea. Defects in this gene have also been linked to intellectual disability. [provided by RefSeq, Mar 2011]

SOBP Gene-Disease associations (from GenCC):

• intellectual disability, anterior maxillary protrusion, and strabismus

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• syndromic intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

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_018013.4. 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
	SOBP	NM_018013.4	MANE Select	c.2232_2233dupGC	p.Pro745ArgfsTer22	frameshift	Exon 6 of 7	NP_060483.3	A7XYQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOBP	ENST00000317357.10	TSL:5 MANE Select	c.2232_2233dupGC	p.Pro745ArgfsTer22	frameshift	Exon 6 of 7	ENSP00000318900.5	A7XYQ1
	SOBP	ENST00000911406.1		c.2232_2233dupGC	p.Pro745ArgfsTer22	frameshift	Exon 6 of 7	ENSP00000581465.1
	SOBP	ENST00000911407.1		c.2232_2233dupGC	p.Pro745ArgfsTer22	frameshift	Exon 6 of 6	ENSP00000581466.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35

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: chr6-107956278;