chr6-42051482-C-T

Variant names:

• chr6-42051482-C-T
• rs1582208473
• NM_138572.3:c.171C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_138572.3(TAF8):​c.171C>T​(p.Ser57Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TAF8 NM_138572.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.34
• Publications: 0 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 6-42051482-C-T is Benign according to our data. Variant chr6-42051482-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 795892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.34 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138572.3. 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
	TAF8	NM_138572.3	MANE Select	c.171C>T	p.Ser57Ser	synonymous	Exon 2 of 9	NP_612639.2	Q7Z7C8-1
	TAF8	NM_001438580.1		c.171C>T	p.Ser57Ser	synonymous	Exon 2 of 10	NP_001425509.1
	TAF8	NM_001410906.1		c.171C>T	p.Ser57Ser	synonymous	Exon 2 of 9	NP_001397835.1	A0A8I5QL44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF8	ENST00000372977.8	TSL:1 MANE Select	c.171C>T	p.Ser57Ser	synonymous	Exon 2 of 9	ENSP00000362068.3	Q7Z7C8-1
	TAF8	ENST00000456846.6	TSL:1	c.171C>T	p.Ser57Ser	synonymous	Exon 2 of 9	ENSP00000411900.2	Q7Z7C8-2
	TAF8	ENST00000372978.7	TSL:1	c.171C>T	p.Ser57Ser	synonymous	Exon 2 of 5	ENSP00000362069.3	A0A0A0MRR3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.1
DANN	Benign	0.84
PhyloP100		-5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1582208473; hg19: chr6-42019220;