17-35822344-CAAAAAAAAAA-CAAAAAAAAAAAAAAA

Variant names:

• chr17-35822344-C-CAAAAA
• rs909362495
• NM_139215.3:c.291-282_291-278dupAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_139215.3(TAF15):​c.291-282_291-278dupAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 67,496 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000015 (0 hom., cov: 30)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 0 publications found

Genes affected

TAF15 (HGNC:11547): (TATA-box binding protein associated factor 15) This gene encodes a member of the TET family of RNA-binding proteins. The encoded protein plays a role in RNA polymerase II gene transcription as a component of a distinct subset of multi-subunit transcription initiation factor TFIID complexes. Translocations involving this gene play a role in acute leukemia and extraskeletal myxoid chondrosarcoma, and mutations in this gene may play a role in amyotrophic lateral sclerosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

TAF15 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000270894 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139215.3. 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
	TAF15	NM_139215.3	MANE Select	c.291-282_291-278dupAAAAA		intron	N/A	NP_631961.1	Q92804-1
	TAF15	NM_003487.4		c.282-282_282-278dupAAAAA		intron	N/A	NP_003478.1	Q92804-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF15	ENST00000605844.6	TSL:1 MANE Select	c.291-296_291-295insAAAAA		intron	N/A	ENSP00000474096.1	Q92804-1
	TAF15	ENST00000604841.5	TSL:1	c.282-296_282-295insAAAAA		intron	N/A	ENSP00000474609.1	Q92804-2
	TAF15	ENST00000603393.6	TSL:1	n.291-296_291-295insAAAAA		intron	N/A	ENSP00000474653.2	A0A075B7E4

Frequencies

GnomAD3 genomes AF: 0.0000148 AC: 1 AN: 67496 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

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: 0.0000341

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000148 AC: 1 AN: 67496 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 31950

African (AFR) AF: 0.00 AC: 0 AN: 20976

American (AMR) AF: 0.00 AC: 0 AN: 6200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1508

East Asian (EAS) AF: 0.00 AC: 0 AN: 2300

South Asian (SAS) AF: 0.00 AC: 0 AN: 2188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 94

European-Non Finnish (NFE) AF: 0.0000341 AC: 1 AN: 29302

Other (OTH) AF: 0.00 AC: 0 AN: 854

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs909362495; hg19: chr17-34149348;