Genetic Variant TAF4B:p.Ala44Thr (chr18-26227063-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005640.3(TAF4B):c.130G>A(p.Ala44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A44P) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TAF4B
NM_005640.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.798

Publications

1 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
spermatogenic failure 13
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TAF4B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12175104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005640.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAF4B	NM_005640.3	MANE Select	c.130G>A	p.Ala44Thr	missense	Exon 1 of 15	NP_005631.1	Q92750-1
TAF4B	NM_001293725.2		c.130G>A	p.Ala44Thr	missense	Exon 1 of 15	NP_001280654.1	J3KTH2
TAF4B	NR_121653.2		n.619G>A		non_coding_transcript_exon	Exon 1 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAF4B	ENST00000269142.10	TSL:1 MANE Select	c.130G>A	p.Ala44Thr	missense	Exon 1 of 15	ENSP00000269142.6	Q92750-1
TAF4B	ENST00000935352.1		c.130G>A	p.Ala44Thr	missense	Exon 1 of 16	ENSP00000605411.1
TAF4B	ENST00000935354.1		c.130G>A	p.Ala44Thr	missense	Exon 1 of 16	ENSP00000605413.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1443048

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718124

African (AFR)

AF:

0.00

AC:

AN:

32108

American (AMR)

AF:

0.00

AC:

AN:

42556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25728

East Asian (EAS)

AF:

0.00

AC:

AN:

38342

South Asian (SAS)

AF:

0.00

AC:

AN:

85124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5470

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107086

Other (OTH)

AF:

0.00

AC:

AN:

59706

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.055

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.80

M_CAP

Benign

0.0095

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

PhyloP100

0.80

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.29

REVEL

Benign

0.021

Sift

Uncertain

0.013

Sift4G

Benign

0.25

Polyphen

0.80

Vest4

0.14

MutPred

0.33

Gain of phosphorylation at A44 (P = 0.0485)

MVP

0.15

MPC

1.3

ClinPred

0.75

GERP RS

1.5

Varity_R

0.052

gMVP

0.32

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over