17-35820543-A-C

Variant names:

• chr17-35820543-A-C
• rs998078616
• NM_139215.3:c.290+106A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139215.3(TAF15):​c.290+106A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000388 in 773,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

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+106A>C		intron	N/A	NP_631961.1	Q92804-1
	TAF15	NM_003487.4		c.281+106A>C		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+106A>C		intron	N/A	ENSP00000474096.1	Q92804-1
	TAF15	ENST00000604841.5	TSL:1	c.281+106A>C		intron	N/A	ENSP00000474609.1	Q92804-2
	TAF15	ENST00000603393.6	TSL:1	n.290+106A>C		intron	N/A	ENSP00000474653.2	A0A075B7E4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000388 AC: 3 AN: 773290 Hom.: 0 AF XY: 0.00000752 AC XY: 3 AN XY: 399104

African (AFR) AF: 0.00 AC: 0 AN: 18118

American (AMR) AF: 0.00 AC: 0 AN: 25440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18484

East Asian (EAS) AF: 0.00 AC: 0 AN: 31562

South Asian (SAS) AF: 0.00 AC: 0 AN: 58848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3990

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 537734

Other (OTH) AF: 0.0000819 AC: 3 AN: 36614

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.069
DANN	Benign	0.45
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs998078616; hg19: chr17-34147547;