chr6-107635075-A-AGCCGCC

Position:

• chr6-107635075-A-AGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 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 (★★).

• 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

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_018013.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOBP	NM_018013.4	c.2247_2252dupGCCGCC	p.Pro750_Pro751dup	disruptive_inframe_insertion	6/7	ENST00000317357.10	NP_060483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10	c.2247_2252dupGCCGCC	p.Pro750_Pro751dup	disruptive_inframe_insertion	6/7	5	NM_018013.4	ENSP00000318900.5
SOBP	ENST00000494935.1	n.102_107dupGCCGCC		non_coding_transcript_exon_variant	1/2	3

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

GnomAD3 exomes AF: 0.000600 AC: 81 AN: 135090 Hom.: 0 AF XY: 0.000670 AC XY: 50 AN XY: 74636

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 SAS exome AF: 0.00113

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

Gnomad4 AFR exome AF: 0.0000312

Gnomad4 AMR exome AF: 0.000238

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00108

Gnomad4 FIN exome AF: 0.000103

Gnomad4 NFE exome AF: 0.000828

Gnomad4 OTH exome AF: 0.000410

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

Gnomad4 AFR AF: 0.000317

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000760

Gnomad4 OTH AF: 0.000961

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 16, 2014

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs541688197; hg19: chr6-107956279;