NM_139215.3:c.291-142A>G

Variant names:

• chr17-35822498-A-G
• rs4251744
• NM_139215.3:c.291-142A>G

Variant summary

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

The NM_139215.3(TAF15):​c.291-142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 723,474 control chromosomes in the GnomAD database, including 3,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1399 hom., cov: 32)
  • Exomes 𝑓: 0.061 (1789 hom.)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.921
• Publications: 1 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 17-35822498-A-G is Benign according to our data. Variant chr17-35822498-A-G is described in ClinVar as Benign. ClinVar VariationId is 1234576.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 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.291-142A>G		intron	N/A	NP_631961.1	Q92804-1
	TAF15	NM_003487.4		c.282-142A>G		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.291-142A>G		intron	N/A	ENSP00000474096.1	Q92804-1
	TAF15	ENST00000604841.5	TSL:1	c.282-142A>G		intron	N/A	ENSP00000474609.1	Q92804-2
	TAF15	ENST00000603393.6	TSL:1	n.291-142A>G		intron	N/A	ENSP00000474653.2	A0A075B7E4

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15929 AN: 152114 Hom.: 1382 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0557

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.0831

GnomAD4 exome AF: 0.0613 AC: 35040 AN: 571242 Hom.: 1789 AF XY: 0.0643 AC XY: 19318 AN XY: 300432

African (AFR) AF: 0.248 AC: 3767 AN: 15192

American (AMR) AF: 0.0349 AC: 859 AN: 24604

Ashkenazi Jewish (ASJ) AF: 0.0255 AC: 412 AN: 16186

East Asian (EAS) AF: 0.00784 AC: 250 AN: 31908

South Asian (SAS) AF: 0.148 AC: 7557 AN: 50958

European-Finnish (FIN) AF: 0.0361 AC: 1186 AN: 32898

Middle Eastern (MID) AF: 0.0396 AC: 91 AN: 2298

European-Non Finnish (NFE) AF: 0.0518 AC: 19001 AN: 366762

Other (OTH) AF: 0.0630 AC: 1917 AN: 30436

GnomAD4 genome AF: 0.105 AC: 15982 AN: 152232 Hom.: 1399 Cov.: 32 AF XY: 0.104 AC XY: 7756 AN XY: 74430

African (AFR) AF: 0.242 AC: 10025 AN: 41480

American (AMR) AF: 0.0555 AC: 850 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3470

East Asian (EAS) AF: 0.0123 AC: 64 AN: 5194

South Asian (SAS) AF: 0.169 AC: 817 AN: 4824

European-Finnish (FIN) AF: 0.0304 AC: 323 AN: 10612

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0529 AC: 3597 AN: 68028

Other (OTH) AF: 0.0822 AC: 174 AN: 2116

Alfa AF: 0.0273 Hom.: 19

Bravo AF: 0.109

Asia WGS AF: 0.110 AC: 381 AN: 3478

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
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.74
PhyloP100		-0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.27		Position offset: -1

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

Other links and lift over

dbSNP: rs4251744; hg19: chr17-34149502;