17-35820316-C-T

Variant names:

• chr17-35820316-C-T
• rs147370557
• NM_139215.3:c.185-16C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_139215.3(TAF15):​c.185-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000916 in 1,613,196 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (1 hom.)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.518
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-35820316-C-T is Benign according to our data. Variant chr17-35820316-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1300617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000579 (846/1460954) while in subpopulation AFR AF = 0.0162 (541/33462). AF 95% confidence interval is 0.015. There are 1 homozygotes in GnomAdExome4. There are 393 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 632 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.185-16C>T		intron	N/A	NP_631961.1	Q92804-1
	TAF15	NM_003487.4		c.176-16C>T		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.185-16C>T		intron	N/A	ENSP00000474096.1	Q92804-1
	TAF15	ENST00000604841.5	TSL:1	c.176-16C>T		intron	N/A	ENSP00000474609.1	Q92804-2
	TAF15	ENST00000603393.6	TSL:1	n.185-16C>T		intron	N/A	ENSP00000474653.2	A0A075B7E4

Frequencies

GnomAD3 genomes AF: 0.00413 AC: 628 AN: 152124 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00117 AC: 295 AN: 251284 AF XY: 0.000854

Gnomad AFR exome AF: 0.0141

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000579 AC: 846 AN: 1460954 Hom.: 1 Cov.: 32 AF XY: 0.000541 AC XY: 393 AN XY: 726836

African (AFR) AF: 0.0162 AC: 541 AN: 33462

American (AMR) AF: 0.00116 AC: 52 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000345 AC: 9 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5766

European-Non Finnish (NFE) AF: 0.000165 AC: 183 AN: 1111194

Other (OTH) AF: 0.000828 AC: 50 AN: 60354

GnomAD4 genome AF: 0.00415 AC: 632 AN: 152242 Hom.: 3 Cov.: 32 AF XY: 0.00388 AC XY: 289 AN XY: 74434

African (AFR) AF: 0.0138 AC: 575 AN: 41544

American (AMR) AF: 0.00177 AC: 27 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67998

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00181 Hom.: 0

Bravo AF: 0.00539

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.1
DANN	Benign	0.54
PhyloP100		0.52

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: rs147370557; hg19: chr17-34147320;