rs3129941

Positions:

• chr6-32369909-A-G
• chr6-32369909-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286474.2(TSBP1):​c.88T>C​(p.Cys30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 1,599,640 control chromosomes in the GnomAD database, including 486,929 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.77 (45206 hom., cov: 31)
  • Exomes 𝑓: 0.78 (441723 hom.)
• Consequence: TSBP1 NM_001286474.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

Genes affected

TSBP1 (HGNC:13922): (testis expressed basic protein 1) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1005486E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSBP1	NM_001286474.2	c.88T>C	p.Cys30Arg	missense_variant	2/26	ENST00000533191.6
TSBP1-AS1	NR_136245.1	n.302+4070A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSBP1	ENST00000533191.6	c.88T>C	p.Cys30Arg	missense_variant	2/26	1	NM_001286474.2	A2
TSBP1-AS1	ENST00000645134.1	n.88-20305A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116786 AN: 151968 Hom.: 45158 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.751

GnomAD3 exomes AF: 0.810 AC: 199703 AN: 246568 Hom.: 81454 AF XY: 0.815 AC XY: 109479 AN XY: 134412

Gnomad AFR exome AF: 0.722

Gnomad AMR exome AF: 0.833

Gnomad ASJ exome AF: 0.803

Gnomad EAS exome AF: 0.850

Gnomad SAS exome AF: 0.891

Gnomad FIN exome AF: 0.853

Gnomad NFE exome AF: 0.780

Gnomad OTH exome AF: 0.780

GnomAD4 exome AF: 0.779 AC: 1127498 AN: 1447554 Hom.: 441723 Cov.: 31 AF XY: 0.784 AC XY: 564821 AN XY: 720792

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.823

Gnomad4 ASJ exome AF: 0.798

Gnomad4 EAS exome AF: 0.927

Gnomad4 SAS exome AF: 0.891

Gnomad4 FIN exome AF: 0.850

Gnomad4 NFE exome AF: 0.761

Gnomad4 OTH exome AF: 0.772

GnomAD4 genome AF: 0.769 AC: 116890 AN: 152086 Hom.: 45206 Cov.: 31 AF XY: 0.775 AC XY: 57625 AN XY: 74364

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.792

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.753

Alfa AF: 0.780 Hom.: 98893

Bravo AF: 0.755

TwinsUK AF: 0.762 AC: 2827

ALSPAC AF: 0.751 AC: 2896

ESP6500AA AF: 0.718 AC: 2171

ESP6500EA AF: 0.761 AC: 4122

ExAC AF: 0.810 AC: 95036

Asia WGS AF: 0.852 AC: 2964 AN: 3478

EpiCase AF: 0.778

EpiControl AF: 0.790

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.030
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.4
DANN	Benign	0.57
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.38	T;.;T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0000011	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
PROVEAN	Benign	2.0	N;N;N;N;.;N;N;.;N;N
REVEL	Benign	0.21
Sift	Benign	1.0	T;T;T;T;.;T;T;.;T;T
Sift4G	Benign	0.89	T;T;T;T;T;T;T;T;.;.
Vest4		0.15
MPC		0.54
ClinPred		0.0026	T
GERP RS		1.8
gMVP		0.020

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

LitVar

Other links and lift over

dbSNP: rs3129941; hg19: chr6-32337686; COSMIC: COSV66658083;