NM_018013.4:c.2238_2252dupGCCGCCGCCGCCGCC

Variant names:

• chr6-107635075-A-AGCCGCCGCCGCCGCC
• rs541688197
• NM_018013.4:c.2238_2252dupGCCGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_018013.4(SOBP):​c.2238_2252dupGCCGCCGCCGCCGCC​(p.Pro747_Pro751dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 149,604 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, 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. Synonymous variant affecting the same amino acid position (i.e. P751P) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 31)
• Consequence: SOBP NM_018013.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• Publications: 1 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: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• syndromic intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018013.4.

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.2238_2252dupGCCGCCGCCGCCGCC	p.Pro747_Pro751dup	disruptive_inframe_insertion	Exon 6 of 7	NP_060483.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOBP	ENST00000317357.10	TSL:5 MANE Select	c.2238_2252dupGCCGCCGCCGCCGCC	p.Pro747_Pro751dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000318900.5
	SOBP	ENST00000911406.1		c.2238_2252dupGCCGCCGCCGCCGCC	p.Pro747_Pro751dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000581465.1
	SOBP	ENST00000911407.1		c.2238_2252dupGCCGCCGCCGCCGCC	p.Pro747_Pro751dup	disruptive_inframe_insertion	Exon 6 of 6	ENSP00000581466.1

Frequencies

GnomAD3 genomes AF: 0.0000201 AC: 3 AN: 149604 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000733

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.0000201 AC: 3 AN: 149604 Hom.: 0 Cov.: 31 AF XY: 0.0000411 AC XY: 3 AN XY: 72932

African (AFR) AF: 0.0000733 AC: 3 AN: 40904

American (AMR) AF: 0.00 AC: 0 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 5046

South Asian (SAS) AF: 0.00 AC: 0 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67132

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
Mutation Taster		=81/19	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs541688197; hg19: chr6-107956279;