rs9268368

Variant names:

• chr6-32366178-T-C
• rs9268368
• NM_001286474.2:c.206A>G

Variant summary

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

The NM_001286474.2(TSBP1):​c.206A>G​(p.Tyr69Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,597,968 control chromosomes in the GnomAD database, including 123,655 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 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 0.34 (9673 hom., cov: 32)
  • Exomes 𝑓: 0.39 (113982 hom.)
• Consequence: TSBP1 NM_001286474.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 55 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=2.4513623E-5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 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.206A>G	p.Tyr69Cys	missense	Exon 6 of 26	NP_001273403.1
	TSBP1	NM_006781.5		c.206A>G	p.Tyr69Cys	missense	Exon 6 of 23	NP_006772.3
	TSBP1	NM_001286475.2		c.196+95A>G		intron	N/A	NP_001273404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSBP1	ENST00000533191.6	TSL:1 MANE Select	c.206A>G	p.Tyr69Cys	missense	Exon 6 of 26	ENSP00000431199.1
	TSBP1	ENST00000442822.6	TSL:1	c.196+95A>G		intron	N/A	ENSP00000411164.2
	TSBP1	ENST00000447241.6	TSL:5	c.206A>G	p.Tyr69Cys	missense	Exon 6 of 23	ENSP00000415517.2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51156 AN: 151990 Hom.: 9657 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.358

GnomAD2 exomes AF: 0.415 AC: 98443 AN: 237068 AF XY: 0.420

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.547

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.378

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.412

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.389 AC: 562733 AN: 1445860 Hom.: 113982 Cov.: 34 AF XY: 0.394 AC XY: 283023 AN XY: 718704

African (AFR) AF: 0.156 AC: 5100 AN: 32792

American (AMR) AF: 0.534 AC: 22622 AN: 42384

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 14332 AN: 25646

East Asian (EAS) AF: 0.333 AC: 13141 AN: 39484

South Asian (SAS) AF: 0.464 AC: 38653 AN: 83292

European-Finnish (FIN) AF: 0.306 AC: 15921 AN: 52070

Middle Eastern (MID) AF: 0.558 AC: 3132 AN: 5608

European-Non Finnish (NFE) AF: 0.386 AC: 427027 AN: 1104934

Other (OTH) AF: 0.382 AC: 22805 AN: 59650

GnomAD4 genome AF: 0.337 AC: 51188 AN: 152108 Hom.: 9673 Cov.: 32 AF XY: 0.337 AC XY: 25041 AN XY: 74358

African (AFR) AF: 0.167 AC: 6918 AN: 41526

American (AMR) AF: 0.446 AC: 6812 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1964 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1910 AN: 5170

South Asian (SAS) AF: 0.428 AC: 2063 AN: 4824

European-Finnish (FIN) AF: 0.297 AC: 3137 AN: 10580

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27137 AN: 67946

Other (OTH) AF: 0.355 AC: 748 AN: 2108

Alfa AF: 0.393 Hom.: 48732

Bravo AF: 0.342

TwinsUK AF: 0.407 AC: 1511

ALSPAC AF: 0.382 AC: 1474

ESP6500AA AF: 0.171 AC: 512

ESP6500EA AF: 0.395 AC: 2126

ExAC AF: 0.413 AC: 48052

Asia WGS AF: 0.342 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.60
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.000025	T
PhyloP100		0.16
Sift4G	Benign	0.43	T
Vest4		0.091
ClinPred		0.0037	T
GERP RS		-0.14
Mutation Taster		=100/0	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: rs9268368; hg19: chr6-32333955;