12-121805199-TC-AA

Position:

• chr12-121805199-TC-AA

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001353345.2(SETD1B):​c.256_257delTCinsAA​(p.Ser86Lys) variant causes a 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SETD1B NM_001353345.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.43

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 3 ACMG points.

• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD1B	NM_001353345.2	c.256_257delTCinsAA	p.Ser86Lys	missense_variant		ENST00000604567.6	NP_001340274.1
SETD1B	XM_024448898.2	c.256_257delTCinsAA	p.Ser86Lys	missense_variant			XP_024304666.1
SETD1B	XM_047428552.1	c.256_257delTCinsAA	p.Ser86Lys	missense_variant			XP_047284508.1
SETD1B	XM_047428553.1	c.256_257delTCinsAA	p.Ser86Lys	missense_variant			XP_047284509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD1B	ENST00000604567.6	c.256_257delTCinsAA	p.Ser86Lys	missense_variant		5	NM_001353345.2	ENSP00000474253.1
SETD1B	ENST00000619791.1	c.256_257delTCinsAA	p.Ser86Lys	missense_variant		1		ENSP00000481531.1
SETD1B	ENST00000542440.5	c.256_257delTCinsAA	p.Ser86Lys	missense_variant		5		ENSP00000442924.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2020

Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

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: chr12-122243105;