6-34877672-T-G

Variant names:

• chr6-34877672-T-G
• rs4646949
• NM_005643.4:c.*918A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005643.4(TAF11):​c.*918A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,144 control chromosomes in the GnomAD database, including 20,791 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (20778 hom., cov: 31)
  • Exomes 𝑓: 0.22 (13 hom.)
• Consequence: TAF11 NM_005643.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454
• Publications: 30 publications found

Genes affected

TAF11 (HGNC:11544): (TATA-box binding protein associated factor 11) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes a small subunit of TFIID that is present in all TFIID complexes and interacts with TBP. This subunit also interacts with another small subunit, TAF13, to form a heterodimer with a structure similar to the histone core structure. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

BLTP3A (HGNC:21216): (bridge-like lipid transfer protein family member 3A) Enables histone deacetylase binding activity and identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005643.4. 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
	TAF11	NM_005643.4	MANE Select	c.*918A>C		3_prime_UTR	Exon 5 of 5	NP_005634.1	Q15544-1
	BLTP3A	NM_017754.4	MANE Select	c.*5234T>G		downstream_gene	N/A	NP_060224.3
	TAF11	NM_001270488.1		c.*992A>C		downstream_gene	N/A	NP_001257417.1	Q15544-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF11	ENST00000361288.9	TSL:1 MANE Select	c.*918A>C		3_prime_UTR	Exon 5 of 5	ENSP00000354633.4	Q15544-1
	TAF11	ENST00000912391.1		c.*918A>C		3_prime_UTR	Exon 5 of 5	ENSP00000582450.1
	TAF11	ENST00000650109.1		c.*1062A>C		3_prime_UTR	Exon 6 of 6	ENSP00000497996.1	A0A3B3ITY8

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69367 AN: 151678 Hom.: 20721 Cov.: 31

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.216 AC: 75 AN: 348 Hom.: 13 Cov.: 0 AF XY: 0.226 AC XY: 48 AN XY: 212

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.213 AC: 73 AN: 342

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.458 AC: 69471 AN: 151796 Hom.: 20778 Cov.: 31 AF XY: 0.457 AC XY: 33868 AN XY: 74162

African (AFR) AF: 0.831 AC: 34383 AN: 41370

American (AMR) AF: 0.392 AC: 5973 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1671 AN: 3470

East Asian (EAS) AF: 0.696 AC: 3577 AN: 5142

South Asian (SAS) AF: 0.423 AC: 2027 AN: 4794

European-Finnish (FIN) AF: 0.211 AC: 2223 AN: 10532

Middle Eastern (MID) AF: 0.462 AC: 134 AN: 290

European-Non Finnish (NFE) AF: 0.269 AC: 18312 AN: 67952

Other (OTH) AF: 0.491 AC: 1036 AN: 2112

Alfa AF: 0.341 Hom.: 33763

Bravo AF: 0.492

Asia WGS AF: 0.546 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.66
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4646949; hg19: chr6-34845449;