17-35822714-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_139215.3(TAF15):c.365A>G(p.Tyr122Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000398 in 1,614,214 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (2 hom.)
• Consequence: TAF15 NM_139215.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.87

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009331882).
• BP6: Variant 17-35822714-A-G is Benign according to our data. Variant chr17-35822714-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 730618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 273 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF15	NM_139215.3	c.365A>G	p.Tyr122Cys	missense_variant	6/16	ENST00000605844.6
TAF15	NM_003487.4	c.356A>G	p.Tyr119Cys	missense_variant	6/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF15	ENST00000605844.6	c.365A>G	p.Tyr122Cys	missense_variant	6/16	1	NM_139215.3	P2
	ENST00000603678.1	n.317-895A>G		intron_variant, non_coding_transcript_variant		5
	ENST00000603981.1	n.264-5773T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00179 AC: 273 AN: 152226 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00625

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000505 AC: 127 AN: 251434 Hom.: 1 AF XY: 0.000361 AC XY: 49 AN XY: 135890

Gnomad AFR exome AF: 0.00634

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000254 AC: 371 AN: 1461870 Hom.: 2 Cov.: 31 AF XY: 0.000217 AC XY: 158 AN XY: 727232

Gnomad4 AFR exome AF: 0.00556

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.00179 AC: 272 AN: 152344 Hom.: 1 Cov.: 32 AF XY: 0.00162 AC XY: 121 AN XY: 74500

Gnomad4 AFR AF: 0.00620

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00110 Hom.: 1

Bravo AF: 0.00210

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00681 AC: 30

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000642 AC: 78

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 13, 2018

- -

TAF15-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 14, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Pathogenic	0.19
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.;T;T;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.0093	T;T;T;T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.9	M;.;.;.;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.76	T
Sift4G	Uncertain	0.0060	D;D;D;T;D
Polyphen		1.0	D;.;.;.;D
Vest4		0.81
MVP		0.97
ClinPred		0.046	T
GERP RS		5.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.13
gMVP		0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs140601071; hg19: chr17-34149718;