18-26227063-GCC-ACG

Variant names:

• chr18-26227063-GCC-ACG
• NM_005640.3:c.130_132delGCCinsACG
• TAF4B p.Ala44Thr

Variant summary

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

The NM_005640.3(TAF4B):​c.130_132delGCCinsACG​(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. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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)
• Consequence: TAF4B NM_005640.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 0 publications found

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)

ACMG classification

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF4B	NM_005640.3	MANE Select	c.130_132delGCCinsACG	p.Ala44Thr	missense	N/A	NP_005631.1	Q92750-1
	TAF4B	NM_001293725.2		c.130_132delGCCinsACG	p.Ala44Thr	missense	N/A	NP_001280654.1	J3KTH2
	TAF4B	NR_121653.2		n.619_621delGCCinsACG		non_coding_transcript_exon	Exon 1 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF4B	ENST00000269142.10	TSL:1 MANE Select	c.130_132delGCCinsACG	p.Ala44Thr	missense	N/A	ENSP00000269142.6	Q92750-1
	TAF4B	ENST00000935352.1		c.130_132delGCCinsACG	p.Ala44Thr	missense	N/A	ENSP00000605411.1
	TAF4B	ENST00000935354.1		c.130_132delGCCinsACG	p.Ala44Thr	missense	N/A	ENSP00000605413.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr18-23807027;