12-121804749-TCACCCCCCC-T

Position:

• chr12-121804749-TCACCCCCCC-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The NM_001353345.2(SETD1B):​c.17_25delCCCCCCACC​(p.Pro6_His8del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000664 in 150,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SETD1B NM_001353345.2 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68

Genes affected

SETD1B (HGNC:29187): (SET domain containing 1B, histone lysine methyltransferase) SET1B is a component of a histone methyltransferase complex that produces trimethylated histone H3 at Lys4 (Lee et al., 2007 [PubMed 17355966]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_001353345.2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD1B	NM_001353345.2	c.17_25delCCCCCCACC	p.Pro6_His8del	disruptive_inframe_deletion	2/17	ENST00000604567.6	NP_001340274.1
SETD1B	XM_024448898.2	c.17_25delCCCCCCACC	p.Pro6_His8del	disruptive_inframe_deletion	2/17		XP_024304666.1
SETD1B	XM_047428552.1	c.17_25delCCCCCCACC	p.Pro6_His8del	disruptive_inframe_deletion	2/17		XP_047284508.1
SETD1B	XM_047428553.1	c.17_25delCCCCCCACC	p.Pro6_His8del	disruptive_inframe_deletion	2/17		XP_047284509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD1B	ENST00000604567.6	c.17_25delCCCCCCACC	p.Pro6_His8del	disruptive_inframe_deletion	2/17	5	NM_001353345.2	ENSP00000474253.1
SETD1B	ENST00000619791.1	c.17_25delCCCCCCACC	p.Pro6_His8del	disruptive_inframe_deletion	1/16	1		ENSP00000481531.1
SETD1B	ENST00000542440.5	c.17_25delCCCCCCACC	p.Pro6_His8del	disruptive_inframe_deletion	2/18	5		ENSP00000442924.1

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150546 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000245

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 Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1397926 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 689472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150666 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73632

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual developmental disorder with seizures and language delay Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Juno Genomics, Hangzhou Juno Genomics, Inc

-

PM2_Supporting+PM4 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-122242655;