17-35820529-CTTTTTT-CTTTTTTTT

Variant names:

• chr17-35820529-C-CTT
• rs879823976
• NM_139215.3:c.290+104_290+105dupTT

Variant summary

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

The NM_139215.3(TAF15):​c.290+104_290+105dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 815,028 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• 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.290+104_290+105dupTT		intron	N/A	NP_631961.1	Q92804-1
	TAF15	NM_003487.4		c.281+104_281+105dupTT		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.290+92_290+93insTT		intron	N/A	ENSP00000474096.1	Q92804-1
	TAF15	ENST00000604841.5	TSL:1	c.281+92_281+93insTT		intron	N/A	ENSP00000474609.1	Q92804-2
	TAF15	ENST00000603393.6	TSL:1	n.290+92_290+93insTT		intron	N/A	ENSP00000474653.2	A0A075B7E4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 144008 Hom.: 0 Cov.: 32

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000193 AC: 157 AN: 815028 Hom.: 0 AF XY: 0.000186 AC XY: 77 AN XY: 413028

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

African (AFR) AF: 0.000220 AC: 4 AN: 18170

American (AMR) AF: 0.000185 AC: 4 AN: 21616

Ashkenazi Jewish (ASJ) AF: 0.000177 AC: 3 AN: 16968

East Asian (EAS) AF: 0.00 AC: 0 AN: 26668

South Asian (SAS) AF: 0.000151 AC: 8 AN: 52944

European-Finnish (FIN) AF: 0.0000546 AC: 2 AN: 36614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3902

European-Non Finnish (NFE) AF: 0.000222 AC: 134 AN: 602418

Other (OTH) AF: 0.0000560 AC: 2 AN: 35728

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 144008 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 69936

African (AFR) AF: 0.00 AC: 0 AN: 39610

American (AMR) AF: 0.00 AC: 0 AN: 14320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3342

East Asian (EAS) AF: 0.00 AC: 0 AN: 5018

South Asian (SAS) AF: 0.00 AC: 0 AN: 4552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65048

Other (OTH) AF: 0.00 AC: 0 AN: 1960

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.025

Splicing

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

Other links and lift over

dbSNP: rs879823976; hg19: chr17-34147533;