NM_005640.3:c.130G>C

Variant names:

• chr18-26227063-G-C
• rs78262333
• NM_005640.3:c.130G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005640.3(TAF4B):​c.130G>C​(p.Ala44Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,595,256 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (67 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (97 hom.)
• Consequence: TAF4B NM_005640.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.798
• Publications: 1 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001581341).
• BP6: Variant 18-26227063-G-C is Benign according to our data. Variant chr18-26227063-G-C is described in ClinVar as Benign. ClinVar VariationId is 778769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

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.130G>C	p.Ala44Pro	missense	Exon 1 of 15	NP_005631.1	Q92750-1
	TAF4B	NM_001293725.2		c.130G>C	p.Ala44Pro	missense	Exon 1 of 15	NP_001280654.1	J3KTH2
	TAF4B	NR_121653.2		n.619G>C		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.130G>C	p.Ala44Pro	missense	Exon 1 of 15	ENSP00000269142.6	Q92750-1
	TAF4B	ENST00000935352.1		c.130G>C	p.Ala44Pro	missense	Exon 1 of 16	ENSP00000605411.1
	TAF4B	ENST00000935354.1		c.130G>C	p.Ala44Pro	missense	Exon 1 of 16	ENSP00000605413.1

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2708 AN: 152094 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00433 AC: 931 AN: 215246 AF XY: 0.00310

Gnomad AFR exome AF: 0.0677

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000136

Gnomad OTH exome AF: 0.00207

GnomAD4 exome AF: 0.00194 AC: 2796 AN: 1443046 Hom.: 97 Cov.: 31 AF XY: 0.00167 AC XY: 1196 AN XY: 718122

African (AFR) AF: 0.0705 AC: 2264 AN: 32108

American (AMR) AF: 0.00338 AC: 144 AN: 42556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25728

East Asian (EAS) AF: 0.00 AC: 0 AN: 38342

South Asian (SAS) AF: 0.000117 AC: 10 AN: 85124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46928

Middle Eastern (MID) AF: 0.00219 AC: 12 AN: 5470

European-Non Finnish (NFE) AF: 0.000107 AC: 118 AN: 1107084

Other (OTH) AF: 0.00415 AC: 248 AN: 59706

GnomAD4 genome AF: 0.0178 AC: 2716 AN: 152210 Hom.: 67 Cov.: 32 AF XY: 0.0172 AC XY: 1282 AN XY: 74418

African (AFR) AF: 0.0625 AC: 2596 AN: 41536

American (AMR) AF: 0.00503 AC: 77 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67996

Other (OTH) AF: 0.0114 AC: 24 AN: 2108

Alfa AF: 0.00741 Hom.: 7

Bravo AF: 0.0196

ESP6500AA AF: 0.0520 AC: 196

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00507 AC: 609

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.80
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.013
Sift	Benign	0.20	T
Sift4G	Benign	0.22	T
Polyphen		0.0060	B
Vest4		0.10
MVP		0.12
MPC		1.0
ClinPred		0.021	T
GERP RS		1.5
Varity_R		0.078
gMVP		0.42
Mutation Taster		=93/7	polymorphism (auto)

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: rs78262333; hg19: chr18-23807027;