1-91977273-G-C

Variant names:

• chr1-91977273-G-C
• rs1684240823
• NM_207189.4:c.849G>C

Variant summary

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

The NM_207189.4(BRDT):​c.849G>C​(p.Met283Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRDT NM_207189.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.89

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRDT	NM_207189.4	c.849G>C	p.Met283Ile	missense_variant	Exon 6 of 19	ENST00000399546.7	NP_997072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRDT	ENST00000399546.7	c.849G>C	p.Met283Ile	missense_variant	Exon 6 of 19	2	NM_207189.4	ENSP00000387822.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.861G>C (p.M287I) alteration is located in exon 6 (coding exon 5) of the BRDT gene. This alteration results from a G to C substitution at nucleotide position 861, causing the methionine (M) at amino acid position 287 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	Pathogenic	0.66
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.;.;T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	.;D;D;D;D;D
M_CAP	Benign	0.0070	T
MetaRNN	Uncertain	0.68	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;.;.;.;.;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.0	D;D;D;.;D;D
REVEL	Benign	0.23
Sift	Benign	0.078	T;T;D;.;D;T
Sift4G	Uncertain	0.0090	D;D;D;D;D;D
Polyphen		0.33	B;.;.;.;.;B
Vest4		0.51
MutPred		0.64		Loss of ubiquitination at K287 (P = 0.0982);.;.;.;Loss of ubiquitination at K287 (P = 0.0982);Loss of ubiquitination at K287 (P = 0.0982);
MVP		0.60
MPC		0.32
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.32
gMVP		0.51

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: rs1684240823; hg19: chr1-92442830;