1-91968164-C-T

Variant names:

• chr1-91968164-C-T
• rs371270716
• NM_207189.4:c.349C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_207189.4(BRDT):​c.349C>T​(p.Leu117Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: BRDT NM_207189.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.196
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10052809).

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.349C>T	p.Leu117Phe	missense	Exon 4 of 19	NP_997072.2	Q58F21-1
	BRDT	NM_001242806.2		c.349C>T	p.Leu117Phe	missense	Exon 4 of 19	NP_001229735.2	Q58F21-3
	BRDT	NM_001242805.2		c.349C>T	p.Leu117Phe	missense	Exon 5 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.349C>T	p.Leu117Phe	missense	Exon 4 of 19	ENSP00000387822.3	Q58F21-1
	BRDT	ENST00000362005.7	TSL:1	c.349C>T	p.Leu117Phe	missense	Exon 5 of 20	ENSP00000354568.3	Q58F21-1
	BRDT	ENST00000402388.1	TSL:1	c.349C>T	p.Leu117Phe	missense	Exon 4 of 19	ENSP00000384051.1	Q58F21-1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152028 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000143 AC: 36 AN: 251268 AF XY: 0.000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000107 AC: 157 AN: 1461662 Hom.: 0 Cov.: 30 AF XY: 0.0000949 AC XY: 69 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000447 AC: 2 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86236

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000120 AC: 133 AN: 1111886

Other (OTH) AF: 0.0000497 AC: 3 AN: 60388

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74374

African (AFR) AF: 0.0000241 AC: 1 AN: 41528

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68014

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000147 Hom.: 0

Bravo AF: 0.0000718

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000189 AC: 23

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.83	L
PhyloP100		0.20
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.046
Sift	Benign	0.16	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.14
MVP		0.60
MPC		0.13
ClinPred		0.047	T
GERP RS		1.6
Varity_R		0.38
gMVP		0.13
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs371270716; hg19: chr1-92433721;