6-107635075-AGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCC

Variant names:

• chr6-107635075-A-AGCCGCC
• rs541688197
• NM_018013.4:c.2247_2252dupGCCGCC

Variant summary

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

The NM_018013.4(SOBP):​c.2247_2252dupGCCGCC​(p.Pro750_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 0.000709 in 1,564,952 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P751P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00073 (1 hom.)
• Consequence: SOBP NM_018013.4 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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: 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.2247_2252dupGCCGCC	p.Pro750_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.2247_2252dupGCCGCC	p.Pro750_Pro751dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000318900.5	A7XYQ1
	SOBP	ENST00000911406.1		c.2247_2252dupGCCGCC	p.Pro750_Pro751dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000581465.1
	SOBP	ENST00000911407.1		c.2247_2252dupGCCGCC	p.Pro750_Pro751dup	disruptive_inframe_insertion	Exon 6 of 6	ENSP00000581466.1

Frequencies

GnomAD3 genomes AF: 0.000481 AC: 72 AN: 149602 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000838

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000760

Gnomad OTH AF: 0.000970

GnomAD2 exomes AF: 0.000600 AC: 81 AN: 135090 AF XY: 0.000670

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000999

Gnomad OTH exome AF: 0.000280

GnomAD4 exome AF: 0.000733 AC: 1037 AN: 1415248 Hom.: 1 Cov.: 33 AF XY: 0.000761 AC XY: 533 AN XY: 700442

African (AFR) AF: 0.0000312 AC: 1 AN: 32002

American (AMR) AF: 0.000238 AC: 9 AN: 37758

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 36750

South Asian (SAS) AF: 0.00108 AC: 88 AN: 81554

European-Finnish (FIN) AF: 0.000103 AC: 5 AN: 48540

Middle Eastern (MID) AF: 0.00142 AC: 8 AN: 5616

European-Non Finnish (NFE) AF: 0.000828 AC: 902 AN: 1089282

Other (OTH) AF: 0.000410 AC: 24 AN: 58542

GnomAD4 genome AF: 0.000488 AC: 73 AN: 149704 Hom.: 0 Cov.: 31 AF XY: 0.000424 AC XY: 31 AN XY: 73044

African (AFR) AF: 0.000317 AC: 13 AN: 41020

American (AMR) AF: 0.000132 AC: 2 AN: 15106

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5032

South Asian (SAS) AF: 0.00105 AC: 5 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: 0.000760 AC: 51 AN: 67120

Other (OTH) AF: 0.000961 AC: 2 AN: 2082

Alfa AF: 0.000221 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

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;