rs10783071

Variant names:

• chr1-91962938-C-A
• rs10783071
• NM_207189.4:c.184C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207189.4(BRDT):​c.184C>A​(p.Gln62Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,585,074 control chromosomes in the GnomAD database, including 663,160 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.85 (56336 hom., cov: 33)
  • Exomes 𝑓: 0.92 (606824 hom.)
• Consequence: BRDT NM_207189.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 26 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.896804E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

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.184C>A	p.Gln62Lys	missense	Exon 2 of 19	NP_997072.2	Q58F21-1
	BRDT	NM_001242806.2		c.184C>A	p.Gln62Lys	missense	Exon 2 of 19	NP_001229735.2	Q58F21-3
	BRDT	NM_001242805.2		c.184C>A	p.Gln62Lys	missense	Exon 3 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.184C>A	p.Gln62Lys	missense	Exon 2 of 19	ENSP00000387822.3	Q58F21-1
	BRDT	ENST00000362005.7	TSL:1	c.184C>A	p.Gln62Lys	missense	Exon 3 of 20	ENSP00000354568.3	Q58F21-1
	BRDT	ENST00000402388.1	TSL:1	c.184C>A	p.Gln62Lys	missense	Exon 2 of 19	ENSP00000384051.1	Q58F21-1

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129662 AN: 152074 Hom.: 56311 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.850

GnomAD2 exomes AF: 0.878 AC: 200165 AN: 227852 AF XY: 0.884

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.885

Gnomad ASJ exome AF: 0.933

Gnomad EAS exome AF: 0.598

Gnomad FIN exome AF: 0.954

Gnomad NFE exome AF: 0.937

Gnomad OTH exome AF: 0.902

GnomAD4 exome AF: 0.917 AC: 1314533 AN: 1432882 Hom.: 606824 Cov.: 34 AF XY: 0.917 AC XY: 652669 AN XY: 712094

African (AFR) AF: 0.683 AC: 21660 AN: 31704

American (AMR) AF: 0.880 AC: 32998 AN: 37516

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 23027 AN: 24744

East Asian (EAS) AF: 0.591 AC: 23128 AN: 39116

South Asian (SAS) AF: 0.845 AC: 67859 AN: 80264

European-Finnish (FIN) AF: 0.954 AC: 50459 AN: 52872

Middle Eastern (MID) AF: 0.904 AC: 5080 AN: 5622

European-Non Finnish (NFE) AF: 0.941 AC: 1037276 AN: 1101932

Other (OTH) AF: 0.897 AC: 53046 AN: 59112

GnomAD4 genome AF: 0.852 AC: 129732 AN: 152192 Hom.: 56336 Cov.: 33 AF XY: 0.854 AC XY: 63506 AN XY: 74402

African (AFR) AF: 0.697 AC: 28886 AN: 41472

American (AMR) AF: 0.879 AC: 13415 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3255 AN: 3472

East Asian (EAS) AF: 0.600 AC: 3110 AN: 5182

South Asian (SAS) AF: 0.837 AC: 4034 AN: 4820

European-Finnish (FIN) AF: 0.956 AC: 10156 AN: 10618

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.940 AC: 63940 AN: 68042

Other (OTH) AF: 0.843 AC: 1783 AN: 2114

Alfa AF: 0.909 Hom.: 301908

Bravo AF: 0.839

TwinsUK AF: 0.941 AC: 3489

ALSPAC AF: 0.945 AC: 3641

ESP6500AA AF: 0.699 AC: 3079

ESP6500EA AF: 0.941 AC: 8096

ExAC AF: 0.875 AC: 106288

Asia WGS AF: 0.729 AC: 2537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.7
DANN	Benign	0.83
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	5.9e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.52	N
PhyloP100		1.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.72	N
REVEL	Benign	0.036
Sift	Benign	0.58	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.037
MPC		0.10
ClinPred		0.0012	T
GERP RS		2.3
Varity_R		0.20
gMVP		0.30
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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

dbSNP: rs10783071; hg19: chr1-92428495; COSMIC: COSV61771206; COSMIC: COSV61771206;