17-35822344-CAAAAAAAAAA-CAAAAAAA

Variant names:

• chr17-35822344-CAAA-C
• rs909362495
• NM_139215.3:c.291-280_291-278delAAA

Variant summary

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

The NM_139215.3(TAF15):​c.291-280_291-278delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 67,478 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00013 (0 hom., cov: 30)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• 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 0 ACMG points.

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.291-280_291-278delAAA		intron	N/A	NP_631961.1	Q92804-1
	TAF15	NM_003487.4		c.282-280_282-278delAAA		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.291-295_291-293delAAA		intron	N/A	ENSP00000474096.1	Q92804-1
	TAF15	ENST00000604841.5	TSL:1	c.282-295_282-293delAAA		intron	N/A	ENSP00000474609.1	Q92804-2
	TAF15	ENST00000603393.6	TSL:1	n.291-295_291-293delAAA		intron	N/A	ENSP00000474653.2	A0A075B7E4

Frequencies

GnomAD3 genomes AF: 0.000133 AC: 9 AN: 67478 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: 0.00221

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: 0.000133 AC: 9 AN: 67478 Hom.: 0 Cov.: 30 AF XY: 0.000188 AC XY: 6 AN XY: 31940

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20978

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: 0.00221 AC: 8 AN: 3614

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

European-Non Finnish (NFE) AF: 0.0000341 AC: 1 AN: 29288

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000443359), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs909362495; hg19: chr17-34149348;