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chr1-91977379-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_207189.4(BRDT):​c.955C>A​(p.Leu319Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000699 in 1,429,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

BRDT
NM_207189.4 missense

Scores

4
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BRDTNM_207189.4 linkuse as main transcriptc.955C>A p.Leu319Ile missense_variant 6/19 ENST00000399546.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BRDTENST00000399546.7 linkuse as main transcriptc.955C>A p.Leu319Ile missense_variant 6/192 NM_207189.4 P1Q58F21-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.99e-7
AC:
1
AN:
1429730
Hom.:
0
Cov.:
30
AF XY:
0.00000141
AC XY:
1
AN XY:
708564
show subpopulations
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:
9.11e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 04, 2022The c.967C>A (p.L323I) alteration is located in exon 6 (coding exon 5) of the BRDT gene. This alteration results from a C to A substitution at nucleotide position 967, causing the leucine (L) at amino acid position 323 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
0.30
BayesDel_addAF
Benign
-0.023
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;.;.;.;T;T
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Benign
0.018
T
MetaRNN
Pathogenic
0.85
D;D;D;D;D;D
MetaSVM
Benign
-0.58
T
MutationAssessor
Uncertain
2.4
M;.;.;.;.;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.8
N;N;N;.;N;N
REVEL
Uncertain
0.33
Sift
Uncertain
0.0020
D;D;D;.;D;D
Sift4G
Uncertain
0.0070
D;D;D;D;D;D
Polyphen
1.0
D;.;.;.;.;D
Vest4
0.71
MutPred
0.78
Gain of methylation at K323 (P = 0.0499);.;.;.;Gain of methylation at K323 (P = 0.0499);Gain of methylation at K323 (P = 0.0499);
MVP
0.75
MPC
0.47
ClinPred
0.96
D
GERP RS
5.9
Varity_R
0.41
gMVP
0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-92442936; API