rs3088232

Variant names:

• chr1-91979700-C-G
• rs3088232
• NM_207189.4:c.1230C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-91979700-C-G
• chr1-91979700-C-T

Variant summary

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

The NM_207189.4(BRDT):​c.1230C>G​(p.Asn410Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,612,400 control chromosomes in the GnomAD database, including 46,807 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.18 (3133 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43674 hom.)
• Consequence: BRDT NM_207189.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219
• Publications: 28 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=0.0022077262).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 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.1230C>G	p.Asn410Lys	missense	Exon 8 of 19	NP_997072.2
	BRDT	NM_001242806.2		c.1242C>G	p.Asn414Lys	missense	Exon 8 of 19	NP_001229735.2
	BRDT	NM_001242805.2		c.1230C>G	p.Asn410Lys	missense	Exon 9 of 20	NP_001229734.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRDT	ENST00000399546.7	TSL:2 MANE Select	c.1230C>G	p.Asn410Lys	missense	Exon 8 of 19	ENSP00000387822.3
	BRDT	ENST00000362005.7	TSL:1	c.1230C>G	p.Asn410Lys	missense	Exon 9 of 20	ENSP00000354568.3
	BRDT	ENST00000402388.1	TSL:1	c.1230C>G	p.Asn410Lys	missense	Exon 8 of 19	ENSP00000384051.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27430 AN: 152018 Hom.: 3122 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.212 AC: 52982 AN: 250326 AF XY: 0.216

Gnomad AFR exome AF: 0.0472

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.0220

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.238 AC: 347928 AN: 1460264 Hom.: 43674 Cov.: 33 AF XY: 0.238 AC XY: 173238 AN XY: 726406

African (AFR) AF: 0.0463 AC: 1549 AN: 33452

American (AMR) AF: 0.220 AC: 9757 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 6435 AN: 26094

East Asian (EAS) AF: 0.0434 AC: 1722 AN: 39680

South Asian (SAS) AF: 0.215 AC: 18465 AN: 85944

European-Finnish (FIN) AF: 0.251 AC: 13393 AN: 53406

Middle Eastern (MID) AF: 0.255 AC: 1468 AN: 5764

European-Non Finnish (NFE) AF: 0.254 AC: 281714 AN: 1111270

Other (OTH) AF: 0.223 AC: 13425 AN: 60330

GnomAD4 genome AF: 0.181 AC: 27462 AN: 152136 Hom.: 3133 Cov.: 32 AF XY: 0.179 AC XY: 13344 AN XY: 74346

African (AFR) AF: 0.0539 AC: 2239 AN: 41546

American (AMR) AF: 0.190 AC: 2897 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 876 AN: 3472

East Asian (EAS) AF: 0.0319 AC: 165 AN: 5176

South Asian (SAS) AF: 0.205 AC: 985 AN: 4812

European-Finnish (FIN) AF: 0.247 AC: 2608 AN: 10558

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17062 AN: 67974

Other (OTH) AF: 0.186 AC: 392 AN: 2110

Alfa AF: 0.217 Hom.: 2479

Bravo AF: 0.170

TwinsUK AF: 0.261 AC: 968

ALSPAC AF: 0.257 AC: 989

ESP6500AA AF: 0.0590 AC: 260

ESP6500EA AF: 0.248 AC: 2137

ExAC AF: 0.211 AC: 25631

Asia WGS AF: 0.115 AC: 399 AN: 3478

EpiCase AF: 0.244

EpiControl AF: 0.246

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.10	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.22
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.040
Sift	Benign	0.28	T
Sift4G	Benign	0.55	T
Polyphen		0.0030	B
Vest4		0.056
MutPred		0.27		Gain of ubiquitination at N410 (P = 0.0054)
MPC		0.091
ClinPred		0.0037	T
GERP RS		3.8
Varity_R		0.12
gMVP		0.070
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3088232; hg19: chr1-92445257; COSMIC: COSV62864533; COSMIC: COSV62864533;