chr18-26227252-C-G

Variant names:

• chr18-26227252-C-G
• rs986737217
• NM_005640.3:c.319C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005640.3(TAF4B):​c.319C>G​(p.Pro107Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAF4B NM_005640.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21206409).

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.319C>G	p.Pro107Ala	missense	Exon 1 of 15	NP_005631.1	Q92750-1
	TAF4B	NM_001293725.2		c.319C>G	p.Pro107Ala	missense	Exon 1 of 15	NP_001280654.1	J3KTH2
	TAF4B	NR_121653.2		n.808C>G		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.319C>G	p.Pro107Ala	missense	Exon 1 of 15	ENSP00000269142.6	Q92750-1
	TAF4B	ENST00000935352.1		c.319C>G	p.Pro107Ala	missense	Exon 1 of 16	ENSP00000605411.1
	TAF4B	ENST00000935354.1		c.319C>G	p.Pro107Ala	missense	Exon 1 of 16	ENSP00000605413.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726750

African (AFR) AF: 0.00 AC: 0 AN: 33348

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111592

Other (OTH) AF: 0.0000166 AC: 1 AN: 60340

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Benign	0.89
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.20	B
Vest4		0.27
MutPred		0.34		Loss of loop (P = 0.0203)
MVP		0.17
MPC		1.8
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.39
gMVP		0.32

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

Other links and lift over

dbSNP: rs986737217; hg19: chr18-23807216;