chr6-32366178-T-C

Position:

• chr6-32366178-T-C

Variant summary

Our verdict is Benign. Variant got -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. 10/13 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 0.34 (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

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=2.4513623E-5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSBP1	NM_001286474.2	c.206A>G	p.Tyr69Cys	missense_variant	6/26	ENST00000533191.6
TSBP1-AS1	NR_136245.1	n.302+339T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSBP1	ENST00000533191.6	c.206A>G	p.Tyr69Cys	missense_variant	6/26	1	NM_001286474.2	A2
TSBP1-AS1	ENST00000645134.1	n.88-24036T>C		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.415 AC: 98443 AN: 237068 Hom.: 21907 AF XY: 0.420 AC XY: 54398 AN XY: 129616

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 SAS exome AF: 0.462

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

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.559

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.382

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

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.355

Alfa AF: 0.408 Hom.: 22137

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 v4.3

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
MutationTaster	Benign	1.0	P;P;P;P;P;P
Sift4G	Benign	0.43	T
Vest4		0.091
ClinPred		0.0037	T
GERP RS		-0.14

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: rs9268368; hg19: chr6-32333955;