7-100107173-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139315.3(TAF6):c.*73T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,508,500 control chromosomes in the GnomAD database, including 254,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24729 hom., cov: 34)
  • Exomes 𝑓: 0.58 (229538 hom.)
• Consequence: TAF6 NM_139315.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0160

Genes affected

AP4M1 (HGNC:574): (adaptor related protein complex 4 subunit mu 1) This gene encodes a subunit of the heterotetrameric AP-4 complex. The encoded protein belongs to the adaptor complexes medium subunits family. This AP-4 complex is involved in the recognition and sorting of cargo proteins with tyrosine-based motifs from the trans-golgi network to the endosomal-lysosomal system. [provided by RefSeq, Jul 2008]

TAF6 (HGNC:11540): (TATA-box binding protein associated factor 6) 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 one of the smaller subunits of TFIID that binds weakly to TBP but strongly to TAF1, the largest subunit of TFIID. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-100107173-A-T is Benign according to our data. Variant chr7-100107173-A-T is described in ClinVar as [Benign]. Clinvar id is 1248740.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP4M1	NM_004722.4	c.*291A>T		3_prime_UTR_variant	15/15	ENST00000359593.9
TAF6	NM_139315.3	c.*73T>A		3_prime_UTR_variant	15/15	ENST00000453269.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP4M1	ENST00000359593.9	c.*291A>T		3_prime_UTR_variant	15/15	1	NM_004722.4	P3
TAF6	ENST00000453269.7	c.*73T>A		3_prime_UTR_variant	15/15	1	NM_139315.3	P1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85767 AN: 152106 Hom.: 24700 Cov.: 34

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.584

GnomAD4 exome AF: 0.578 AC: 784244 AN: 1356276 Hom.: 229538 Cov.: 29 AF XY: 0.582 AC XY: 387151 AN XY: 665160

Gnomad4 AFR exome AF: 0.474

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.867

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.569

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 0.593

GnomAD4 genome AF: 0.564 AC: 85854 AN: 152224 Hom.: 24729 Cov.: 34 AF XY: 0.571 AC XY: 42469 AN XY: 74404

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.588

Alfa AF: 0.538 Hom.: 2775

Bravo AF: 0.566

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.58
Dann	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs13309; hg19: chr7-99704796;