chr1-91962764-C-T

Position:

• chr1-91962764-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207189.4(BRDT):​c.10C>T​(p.Pro4Ser) 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. 14/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BRDT NM_207189.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.913

Genes affected

BRDT (HGNC:1105): (bromodomain testis associated) BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Several transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118985385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRDT	NM_207189.4	c.10C>T	p.Pro4Ser	missense_variant	2/19	ENST00000399546.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRDT	ENST00000399546.7	c.10C>T	p.Pro4Ser	missense_variant	2/19	2	NM_207189.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1433312 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 712166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000756

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

Jan 23, 2024

The c.10C>T (p.P4S) alteration is located in exon 2 (coding exon 1) of the BRDT gene. This alteration results from a C to T substitution at nucleotide position 10, causing the proline (P) at amino acid position 4 to be replaced by a serine (S). 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	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.32	T;.;.;.;.;.;.;.;.;T;.;.;.;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	N;N;N;.;.;.;.;.;.;.;.;.;.;N
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-4.8	D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.050
Sift	Benign	0.076	T;T;T;T;T;T;T;.;T;T;T;T;.;T
Sift4G	Benign	0.21	T;T;T;T;T;T;T;.;T;T;T;T;T;T
Polyphen		0.0070	B;.;.;.;.;.;.;.;.;.;.;.;.;B
Vest4		0.12
MVP		0.45
MPC		0.083
ClinPred		0.33	T
GERP RS		1.6
Varity_R		0.081
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1682624277; hg19: chr1-92428321;