18-26293530-C-T

Position:

• chr18-26293530-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_005640.3(TAF4B):​c.1831C>T​(p.Arg611*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000577 in 1,386,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: TAF4B NM_005640.3 stop_gained, splice_region
• Scores: Splicing: ADA: 0.01925
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.54

Genes affected

TAF4B (HGNC:11538): (TATA-box binding protein associated factor 4b) TATA binding protein (TBP) and TBP-associated factors (TAFs) participate in the formation of the TFIID protein complex, which is involved in initiation of transcription of genes by RNA polymerase II. This gene encodes a cell type-specific TAF that may be responsible for mediating transcription by a subset of activators in B cells. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

TAF4B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 18-26293530-C-T is Pathogenic according to our data. Variant chr18-26293530-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 135657.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr18-26293530-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF4B	NM_005640.3	c.1831C>T	p.Arg611*	stop_gained, splice_region_variant	9/15	ENST00000269142.10	NP_005631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF4B	ENST00000269142.10	c.1831C>T	p.Arg611*	stop_gained, splice_region_variant	9/15	1	NM_005640.3	ENSP00000269142.6
TAF4B	ENST00000578121.5	c.1846C>T	p.Arg616*	stop_gained, splice_region_variant	9/15	2		ENSP00000462980.1
TAF4B	ENST00000418698.3	n.1831C>T		splice_region_variant, non_coding_transcript_exon_variant	9/16	5		ENSP00000389365.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000577 AC: 8 AN: 1386984 Hom.: 0 Cov.: 25 AF XY: 0.00000579 AC XY: 4 AN XY: 690630

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000648

Gnomad4 OTH exome AF: 0.0000176

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 13 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.69	D
Vest4		0.86
ClinPred		1.0	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.019
dbscSNV1_RF	Benign	0.32
SpliceAI score (max)		0.020		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: rs587777427; hg19: chr18-23873494;