17-35820529-CTTTTTT-CTTTTTTT

Variant names:

• chr17-35820529-C-CT
• rs879823976
• NM_139215.3:c.290+105dupT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_139215.3(TAF15):​c.290+105dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 912,880 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 0.00088 (0 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 127 AD gene.

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+105dupT		intron	N/A	NP_631961.1	Q92804-1
	TAF15	NM_003487.4		c.281+105dupT		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+93insT		intron	N/A	ENSP00000474096.1	Q92804-1
	TAF15	ENST00000604841.5	TSL:1	c.281+92_281+93insT		intron	N/A	ENSP00000474609.1	Q92804-2
	TAF15	ENST00000603393.6	TSL:1	n.290+92_290+93insT		intron	N/A	ENSP00000474653.2	A0A075B7E4

Frequencies

GnomAD3 genomes AF: 0.000848 AC: 122 AN: 143938 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000934

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00180

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.00134

Gnomad MID AF: 0.00336

Gnomad NFE AF: 0.000615

Gnomad OTH AF: 0.00153

GnomAD4 exome AF: 0.0423 AC: 32526 AN: 768890 Hom.: 0 AF XY: 0.0426 AC XY: 16553 AN XY: 388610

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

African (AFR) AF: 0.0310 AC: 532 AN: 17142

American (AMR) AF: 0.0402 AC: 801 AN: 19918

Ashkenazi Jewish (ASJ) AF: 0.0454 AC: 711 AN: 15674

East Asian (EAS) AF: 0.0377 AC: 902 AN: 23904

South Asian (SAS) AF: 0.0399 AC: 1939 AN: 48556

European-Finnish (FIN) AF: 0.0374 AC: 1260 AN: 33646

Middle Eastern (MID) AF: 0.0303 AC: 113 AN: 3732

European-Non Finnish (NFE) AF: 0.0434 AC: 24865 AN: 572992

Other (OTH) AF: 0.0421 AC: 1403 AN: 33326

⚠️ 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 AF: 0.000882 AC: 127 AN: 143990 Hom.: 0 Cov.: 32 AF XY: 0.000815 AC XY: 57 AN XY: 69968

African (AFR) AF: 0.000957 AC: 38 AN: 39690

American (AMR) AF: 0.00112 AC: 16 AN: 14326

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 6 AN: 3342

East Asian (EAS) AF: 0.00120 AC: 6 AN: 5002

South Asian (SAS) AF: 0.000221 AC: 1 AN: 4532

European-Finnish (FIN) AF: 0.00134 AC: 12 AN: 8958

Middle Eastern (MID) AF: 0.00365 AC: 1 AN: 274

European-Non Finnish (NFE) AF: 0.000615 AC: 40 AN: 65014

Other (OTH) AF: 0.00355 AC: 7 AN: 1972

Alfa AF: 0.0000561 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.025
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs879823976; hg19: chr17-34147533;