6-42057457-C-G

Position:

• chr6-42057457-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_138572.3(TAF8):​c.433C>G​(p.His145Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TAF8 NM_138572.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF8	NM_138572.3	c.433C>G	p.His145Asp	missense_variant	5/9	ENST00000372977.8	NP_612639.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF8	ENST00000372977.8	c.433C>G	p.His145Asp	missense_variant	5/9	1	NM_138572.3	ENSP00000362068.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, Cologne University

Oct 05, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.;.;.;D;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;.;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.1	.;M;M;M;M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.9	D;D;D;D;D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0060	D;.;D;.;D;D
Sift4G	Uncertain	0.018	D;D;D;D;D;T
Polyphen		0.97, 0.99, 0.99, 1.0	.;D;D;D;D;D
Vest4		0.64
MutPred		0.70		Loss of catalytic residue at H145 (P = 0.0775);Loss of catalytic residue at H145 (P = 0.0775);Loss of catalytic residue at H145 (P = 0.0775);Loss of catalytic residue at H145 (P = 0.0775);Loss of catalytic residue at H145 (P = 0.0775);.;
MVP		0.50
MPC		1.1
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-42025195;