1-91977043-G-A

Variant names:

• chr1-91977043-G-A
• NM_207189.4:c.619G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 17/24 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
• Publications: 0 publications found

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]

BRDT Gene-Disease associations (from GenCC):

• spermatogenic failure 21

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.121780336).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207189.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRDT	NM_207189.4	MANE Select	c.619G>A	p.Val207Ile	missense splice_region	Exon 6 of 19	NP_997072.2	Q58F21-1
	BRDT	NM_001242806.2		c.631G>A	p.Val211Ile	missense splice_region	Exon 6 of 19	NP_001229735.2	Q58F21-3
	BRDT	NM_001242805.2		c.619G>A	p.Val207Ile	missense splice_region	Exon 7 of 20	NP_001229734.2	Q58F21-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRDT	ENST00000399546.7	TSL:2 MANE Select	c.619G>A	p.Val207Ile	missense splice_region	Exon 6 of 19	ENSP00000387822.3	Q58F21-1
	BRDT	ENST00000362005.7	TSL:1	c.619G>A	p.Val207Ile	missense splice_region	Exon 7 of 20	ENSP00000354568.3	Q58F21-1
	BRDT	ENST00000402388.1	TSL:1	c.619G>A	p.Val207Ile	missense splice_region	Exon 6 of 19	ENSP00000384051.1	Q58F21-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.032
Sift	Benign	0.44	T
Sift4G	Benign	0.40	T
Polyphen		0.012	B
Vest4		0.028
MutPred		0.18		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
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr1-92442600;