rs9381135

Variant names:

• chr6-42083085-C-T
• rs9381135
• NM_138572.3:c.*5540C>T

Variant summary

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

The NM_138572.3(TAF8):​c.*5540C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,190 control chromosomes in the GnomAD database, including 1,380 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 0.13 (1380 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TAF8 NM_138572.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 4 publications found

Genes affected

TAF8 (HGNC:17300): (TATA-box binding protein associated factor 8) This gene encodes one of several TATA-binding protein (TBP)-associated factors (TAFs), which are integral subunits of the general transcription factor complex TFIID. TFIID recognizes the core promoter of many genes and nucleates the assembly of a transcription preinitiation complex containing RNA polymerase II and other initiation factors. The protein encoded by this gene contains an H4-like histone fold domain, and interacts with several subunits of TFIID including TBP and the histone-fold protein TAF10. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

TAF8 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF8	NM_138572.3	c.*5540C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000372977.8	NP_612639.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF8	ENST00000372977.8	c.*5540C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_138572.3	ENSP00000362068.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19898 AN: 152072 Hom.: 1382 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.128

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.131 AC: 19914 AN: 152190 Hom.: 1380 Cov.: 32 AF XY: 0.130 AC XY: 9666 AN XY: 74408

African (AFR) AF: 0.144 AC: 5989 AN: 41514

American (AMR) AF: 0.0855 AC: 1309 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1248 AN: 5184

South Asian (SAS) AF: 0.196 AC: 947 AN: 4826

European-Finnish (FIN) AF: 0.0876 AC: 927 AN: 10578

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8615 AN: 67996

Other (OTH) AF: 0.130 AC: 274 AN: 2114

Alfa AF: 0.131 Hom.: 2961

Bravo AF: 0.131

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.59
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs9381135; hg19: chr6-42050823;