chr12-121805845-TCT-A

Position:

• chr12-121805845-TCT-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP2 PP5

The NM_001353345.2(SETD1B):​c.284_286delTCTinsA​(p.Phe95fs) variant causes a frameshift, stop gained, missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SETD1B NM_001353345.2 frameshift, stop_gained, missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.96

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SETD1B. . Trascript score misZ 3.1492 (greater than threshold 3.09). GenCC has associacion of gene with intellectual developmental disorder with seizures and language delay.
• PP5: Variant 12-121805845-TCT-A is Pathogenic according to our data. Variant chr12-121805845-TCT-A is described in ClinVar as [Pathogenic]. Clinvar id is 2498278.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD1B	NM_001353345.2	c.284_286delTCTinsA	p.Phe95fs	frameshift_variant, stop_gained, missense_variant	4/17	ENST00000604567.6	NP_001340274.1
SETD1B	XM_024448898.2	c.284_286delTCTinsA	p.Phe95fs	frameshift_variant, stop_gained, missense_variant	4/17		XP_024304666.1
SETD1B	XM_047428552.1	c.284_286delTCTinsA	p.Phe95fs	frameshift_variant, stop_gained, missense_variant	4/17		XP_047284508.1
SETD1B	XM_047428553.1	c.284_286delTCTinsA	p.Phe95fs	frameshift_variant, stop_gained, missense_variant	4/17		XP_047284509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD1B	ENST00000604567.6	c.284_286delTCTinsA	p.Phe95fs	frameshift_variant, stop_gained, missense_variant	4/17	5	NM_001353345.2	ENSP00000474253.1
SETD1B	ENST00000619791.1	c.284_286delTCTinsA	p.Phe95fs	frameshift_variant, stop_gained, missense_variant	3/16	1		ENSP00000481531.1
SETD1B	ENST00000542440.5	c.284_286delTCTinsA	p.Phe95fs	frameshift_variant, stop_gained, missense_variant	4/18	5		ENSP00000442924.1

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual developmental disorder with seizures and language delay Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 14, 2023

- -

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: chr12-122243751;