rs1265754

Variant names:

• chr6-32335915-T-A
• rs1265754
• NM_001286474.2:c.400A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32335915-T-A
• chr6-32335915-T-C

Variant summary

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

The NM_001286474.2(TSBP1):​c.400A>T​(p.Ile134Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 1,606,862 control chromosomes in the GnomAD database, including 9,765 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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 0.063 (461 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9304 hom.)
• Consequence: TSBP1 NM_001286474.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020620227).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286474.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSBP1	NM_001286474.2	MANE Select	c.400A>T	p.Ile134Phe	missense	Exon 14 of 26	NP_001273403.1
	TSBP1	NM_006781.5		c.448A>T	p.Ile150Phe	missense	Exon 13 of 23	NP_006772.3
	TSBP1	NM_001286475.2		c.379A>T	p.Ile127Phe	missense	Exon 13 of 24	NP_001273404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSBP1	ENST00000533191.6	TSL:1 MANE Select	c.400A>T	p.Ile134Phe	missense	Exon 14 of 26	ENSP00000431199.1
	TSBP1	ENST00000442822.6	TSL:1	c.379A>T	p.Ile127Phe	missense	Exon 13 of 26	ENSP00000411164.2
	TSBP1	ENST00000447241.6	TSL:5	c.448A>T	p.Ile150Phe	missense	Exon 13 of 23	ENSP00000415517.2

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9547 AN: 152152 Hom.: 461 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0848

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0455

GnomAD2 exomes AF: 0.0587 AC: 14227 AN: 242528 AF XY: 0.0581

Gnomad AFR exome AF: 0.0162

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0362

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0819

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.0613

GnomAD4 exome AF: 0.0997 AC: 145081 AN: 1454592 Hom.: 9304 Cov.: 29 AF XY: 0.0963 AC XY: 69715 AN XY: 724088

African (AFR) AF: 0.0157 AC: 525 AN: 33436

American (AMR) AF: 0.0225 AC: 1004 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 1032 AN: 26096

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39662

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86160

European-Finnish (FIN) AF: 0.0857 AC: 4409 AN: 51450

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5764

European-Non Finnish (NFE) AF: 0.120 AC: 132873 AN: 1107140

Other (OTH) AF: 0.0859 AC: 5173 AN: 60190

GnomAD4 genome AF: 0.0627 AC: 9544 AN: 152270 Hom.: 461 Cov.: 32 AF XY: 0.0584 AC XY: 4348 AN XY: 74444

African (AFR) AF: 0.0165 AC: 684 AN: 41566

American (AMR) AF: 0.0286 AC: 438 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0380 AC: 132 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.0848 AC: 899 AN: 10606

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7238 AN: 68014

Other (OTH) AF: 0.0450 AC: 95 AN: 2110

Alfa AF: 0.0846 Hom.: 447

Bravo AF: 0.0571

TwinsUK AF: 0.126 AC: 469

ALSPAC AF: 0.125 AC: 483

ESP6500AA AF: 0.0222 AC: 67

ESP6500EA AF: 0.103 AC: 558

ExAC AF: 0.0597 AC: 7033

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.0927

EpiControl AF: 0.0859

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Benign	0.95
Eigen	Benign	-0.048
Eigen_PC	Benign	-0.067
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.96
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.061
Sift	Benign	0.071	T
Sift4G	Uncertain	0.048	D
Vest4		0.58
MPC		0.49
ClinPred		0.024	T
GERP RS		3.0
gMVP		0.054
Mutation Taster		=94/6	polymorphism (auto)

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: rs1265754; hg19: chr6-32303692; COSMIC: COSV100898840; COSMIC: COSV100898840;