chr1-91977043-G-A

Position:

• chr1-91977043-G-A

Variant summary

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

The NM_207189.4(BRDT):​c.619G>A​(p.Val207Ile) variant causes a missense, splice region 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. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRDT NM_207189.4 missense, splice_region
• Scores: Splicing: ADA: 0.01204
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54

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=0.121780336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRDT	NM_207189.4	c.619G>A	p.Val207Ile	missense_variant, splice_region_variant	6/19	ENST00000399546.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRDT	ENST00000399546.7	c.619G>A	p.Val207Ile	missense_variant, splice_region_variant	6/19	2	NM_207189.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Oct 03, 2023

The c.631G>A (p.V211I) alteration is located in exon 6 (coding exon 5) of the BRDT gene. This alteration results from a G to A substitution at nucleotide position 631, causing the valine (V) at amino acid position 211 to be replaced by an isoleucine (I). 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	0.082
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.061	T;.;.;.;T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L;.;.;.;.;L
MutationTaster	Benign	0.97	N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.55	N;N;N;N;N;N
REVEL	Benign	0.032
Sift	Benign	0.44	T;T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T;T
Polyphen		0.012	B;.;.;.;.;B
Vest4		0.028
MutPred		0.18		Loss of ubiquitination at K212 (P = 0.1106);.;.;.;Loss of ubiquitination at K212 (P = 0.1106);Loss of ubiquitination at K212 (P = 0.1106);
MVP		0.55
MPC		0.066
ClinPred		0.11	T
GERP RS		3.3
Varity_R		0.027
gMVP		0.084

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.012
dbscSNV1_RF	Benign	0.20
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-92442600;