17-35820529-CT-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_139215.3(TAF15):​c.290+105delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 821,506 control chromosomes in the GnomAD database, including 295 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (260 hom., cov: 32)
  • Exomes 𝑓: 0.18 (35 hom.)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-35820529-CT-C is Benign according to our data. Variant chr17-35820529-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1265877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5110 AN: 143564 Hom.: 260 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.00688

Gnomad EAS AF: 0.00260

Gnomad SAS AF: 0.00110

Gnomad FIN AF: 0.00959

Gnomad MID AF: 0.0268

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.0262

GnomAD4 exome AF: 0.177 AC: 119759 AN: 677890 Hom.: 35 AF XY: 0.181 AC XY: 61652 AN XY: 339838

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

African (AFR) AF: 0.268 AC: 4109 AN: 15308

American (AMR) AF: 0.254 AC: 4191 AN: 16470

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 3011 AN: 13124

East Asian (EAS) AF: 0.260 AC: 4785 AN: 18420

South Asian (SAS) AF: 0.232 AC: 9255 AN: 39822

European-Finnish (FIN) AF: 0.203 AC: 5672 AN: 27946

Middle Eastern (MID) AF: 0.150 AC: 510 AN: 3390

European-Non Finnish (NFE) AF: 0.160 AC: 82551 AN: 515216

Other (OTH) AF: 0.201 AC: 5675 AN: 28194

⚠️ 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: 0.0357 AC: 5120 AN: 143616 Hom.: 260 Cov.: 32 AF XY: 0.0342 AC XY: 2385 AN XY: 69714

African (AFR) AF: 0.115 AC: 4546 AN: 39654

American (AMR) AF: 0.0148 AC: 211 AN: 14304

Ashkenazi Jewish (ASJ) AF: 0.00688 AC: 23 AN: 3342

East Asian (EAS) AF: 0.00261 AC: 13 AN: 4990

South Asian (SAS) AF: 0.00110 AC: 5 AN: 4530

European-Finnish (FIN) AF: 0.00959 AC: 85 AN: 8864

Middle Eastern (MID) AF: 0.0255 AC: 7 AN: 274

European-Non Finnish (NFE) AF: 0.00276 AC: 179 AN: 64814

Other (OTH) AF: 0.0260 AC: 51 AN: 1964

Alfa AF: 0.000393 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.025

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: rs879823976; hg19: chr17-34147533;