chr7-100107204-A-G

Position:

• chr7-100107204-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139315.3(TAF6):​c.*42T>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 0.578 in 1,518,228 control chromosomes in the GnomAD database, including 258,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (23213 hom., cov: 34)
  • Exomes 𝑓: 0.58 (234885 hom.)
• Consequence: TAF6 NM_139315.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.99

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-100107204-A-G is Benign according to our data. Variant chr7-100107204-A-G is described in ClinVar as [Benign]. Clinvar id is 1260154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP4M1	NM_004722.4	c.*322A>G		3_prime_UTR_variant	15/15	ENST00000359593.9
TAF6	NM_139315.3	c.*42T>C		3_prime_UTR_variant	15/15	ENST00000453269.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP4M1	ENST00000359593.9	c.*322A>G		3_prime_UTR_variant	15/15	1	NM_004722.4	P3
TAF6	ENST00000453269.7	c.*42T>C		3_prime_UTR_variant	15/15	1	NM_139315.3	P1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82086 AN: 152088 Hom.: 23201 Cov.: 34

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.565

GnomAD3 exomes AF: 0.603 AC: 105746 AN: 175400 Hom.: 32891 AF XY: 0.607 AC XY: 56175 AN XY: 92594

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.652

Gnomad ASJ exome AF: 0.639

Gnomad EAS exome AF: 0.884

Gnomad SAS exome AF: 0.686

Gnomad FIN exome AF: 0.580

Gnomad NFE exome AF: 0.565

Gnomad OTH exome AF: 0.605

GnomAD4 exome AF: 0.582 AC: 795404 AN: 1366026 Hom.: 234885 Cov.: 44 AF XY: 0.586 AC XY: 392516 AN XY: 669482

Gnomad4 AFR exome AF: 0.371

Gnomad4 AMR exome AF: 0.652

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.869

Gnomad4 SAS exome AF: 0.687

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.592

GnomAD4 genome AF: 0.540 AC: 82136 AN: 152202 Hom.: 23213 Cov.: 34 AF XY: 0.548 AC XY: 40773 AN XY: 74416

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.568

Alfa AF: 0.534 Hom.: 7794

Bravo AF: 0.538

Asia WGS AF: 0.764 AC: 2656 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Alazami-Yuan syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.67
DANN	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1050542; hg19: chr7-99704827; COSMIC: COSV59842009; COSMIC: COSV59842009;