NM_018013.4:c.2244_2252dupGCCGCCGCC

Variant names:

• chr6-107635075-A-AGCCGCCGCC
• rs541688197
• NM_018013.4:c.2244_2252dupGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM4 BS2

The NM_018013.4(SOBP):​c.2244_2252dupGCCGCCGCC​(p.Pro749_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 0.000265 in 1,564,954 control chromosomes in the GnomAD database, including 4 homozygotes. 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 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00028 (4 hom.)
• 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: 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: Likely_benign. The variant received -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018013.4.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR,Unknown gene

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.2244_2252dupGCCGCCGCC	p.Pro749_Pro751dup	disruptive_inframe_insertion	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.2244_2252dupGCCGCCGCC	p.Pro749_Pro751dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000318900.5	A7XYQ1
	SOBP	ENST00000911406.1		c.2244_2252dupGCCGCCGCC	p.Pro749_Pro751dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000581465.1
	SOBP	ENST00000911407.1		c.2244_2252dupGCCGCCGCC	p.Pro749_Pro751dup	disruptive_inframe_insertion	Exon 6 of 6	ENSP00000581466.1

Frequencies

GnomAD3 genomes AF: 0.000160 AC: 24 AN: 149604 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000489

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00297

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000745

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000148 AC: 20 AN: 135090 AF XY: 0.000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00169

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000555

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000276 AC: 391 AN: 1415248 Hom.: 4 Cov.: 33 AF XY: 0.000257 AC XY: 180 AN XY: 700448

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000625 AC: 2 AN: 32002

American (AMR) AF: 0.00 AC: 0 AN: 37758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25204

East Asian (EAS) AF: 0.00994 AC: 365 AN: 36734

South Asian (SAS) AF: 0.0000736 AC: 6 AN: 81554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48540

Middle Eastern (MID) AF: 0.000356 AC: 2 AN: 5618

European-Non Finnish (NFE) AF: 0.0000119 AC: 13 AN: 1089296

Other (OTH) AF: 0.0000512 AC: 3 AN: 58542

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000160 AC: 24 AN: 149706 Hom.: 0 Cov.: 31 AF XY: 0.000192 AC XY: 14 AN XY: 73046

African (AFR) AF: 0.0000488 AC: 2 AN: 41020

American (AMR) AF: 0.0000662 AC: 1 AN: 15106

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

East Asian (EAS) AF: 0.00298 AC: 15 AN: 5032

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4766

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000745 AC: 5 AN: 67122

Other (OTH) AF: 0.00 AC: 0 AN: 2082

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;