3-9428972-TCA-CTT

Variant names:

• chr3-9428972-TCA-CTT
• NM_001080517.3:c.34_36delTCAinsCTT
• SETD5 p.Ser12Leu

Variant summary

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

The NM_001080517.3(SETD5):​c.34_36delTCAinsCTT​(p.Ser12Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SETD5 NM_001080517.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.29
• Publications: 0 publications found

Genes affected

SETD5 (HGNC:25566): (SET domain containing 5) This function of this gene has yet to be determined but based on sequence similarity to other SET domain proteins it may function as a histone methyltransferase. Mutations in this gene have been associated with an autosomal dominant form of intellectual disability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

SETD5 Gene-Disease associations (from GenCC):

• intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080517.3. 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
	SETD5	NM_001080517.3	MANE Select	c.34_36delTCAinsCTT	p.Ser12Leu	missense	N/A	NP_001073986.1	Q9C0A6-1
	SETD5	NM_001437635.1		c.34_36delTCAinsCTT	p.Ser12Leu	missense	N/A	NP_001424564.1
	SETD5	NM_001437633.1		c.34_36delTCAinsCTT	p.Ser12Leu	missense	N/A	NP_001424562.1	A0A804HKJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD5	ENST00000402198.7	TSL:5 MANE Select	c.34_36delTCAinsCTT	p.Ser12Leu	missense	N/A	ENSP00000385852.2	Q9C0A6-1
	SETD5	ENST00000682536.1		c.34_36delTCAinsCTT	p.Ser12Leu	missense	N/A	ENSP00000507956.1	A0A804HKJ9
	SETD5	ENST00000866906.1		c.34_36delTCAinsCTT	p.Ser12Leu	missense	N/A	ENSP00000536965.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-9470656;