5-138149730-T-C

Position:

• chr5-138149730-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139199.2(BRD8):​c.3188A>G​(p.Gln1063Arg) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: BRD8 NM_139199.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

Genes affected

BRD8 (HGNC:19874): (bromodomain containing 8) The protein encoded by this gene interacts with thyroid hormone receptor in a ligand-dependent manner and enhances thyroid hormone-dependent activation from thyroid response elements. This protein contains a bromodomain and is thought to be a nuclear receptor coactivator. Multiple alternatively spliced transcript variants that encode distinct isoforms have been identified. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD8	NM_139199.2	c.3188A>G	p.Gln1063Arg	missense_variant	23/27	ENST00000254900.10	NP_631938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRD8	ENST00000254900.10	c.3188A>G	p.Gln1063Arg	missense_variant	23/27	1	NM_139199.2	ENSP00000254900	P1
BRD8	ENST00000427976.1	c.506A>G	p.Gln169Arg	missense_variant	3/6	3		ENSP00000392646

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2023

The c.3188A>G (p.Q1063R) alteration is located in exon 23 (coding exon 23) of the BRD8 gene. This alteration results from a A to G substitution at nucleotide position 3188, causing the glutamine (Q) at amino acid position 1063 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.0059	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.030
Sift	Benign	0.11	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0	B;.
Vest4		0.18
MutPred		0.17		Gain of phosphorylation at S1066 (P = 0.0912);.;
MVP		0.23
MPC		0.13
ClinPred		0.046	T
GERP RS		0.94
Varity_R		0.034
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-137485419;