NM_001286474.2:c.1192A>C

Variant names:

• chr6-32293475-T-G
• rs7775397
• NM_001286474.2:c.1192A>C

Variant summary

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

The NM_001286474.2(TSBP1):​c.1192A>C​(p.Lys398Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 1,612,968 control chromosomes in the GnomAD database, including 9,852 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.

• Frequency:
  • Genomes: 𝑓 0.063 (456 hom., cov: 31)
  • Exomes 𝑓: 0.10 (9396 hom.)
• Consequence: TSBP1 NM_001286474.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

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=0.0019672513).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSBP1	NM_001286474.2	c.1192A>C	p.Lys398Gln	missense_variant	Exon 26 of 26	ENST00000533191.6	NP_001273403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSBP1	ENST00000533191.6	c.1192A>C	p.Lys398Gln	missense_variant	Exon 26 of 26	1	NM_001286474.2	ENSP00000431199.1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9525 AN: 152118 Hom.: 456 Cov.: 31

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: 0.0842

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0470

GnomAD3 exomes AF: 0.0595 AC: 14684 AN: 246618 Hom.: 777 AF XY: 0.0587 AC XY: 7880 AN XY: 134330

Gnomad AFR exome AF: 0.0162

Gnomad AMR exome AF: 0.0219

Gnomad ASJ exome AF: 0.0363

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000658

Gnomad FIN exome AF: 0.0818

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.0609

GnomAD4 exome AF: 0.101 AC: 146917 AN: 1460732 Hom.: 9396 Cov.: 34 AF XY: 0.0970 AC XY: 70493 AN XY: 726680

Gnomad4 AFR exome AF: 0.0158

Gnomad4 AMR exome AF: 0.0226

Gnomad4 ASJ exome AF: 0.0397

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.0857

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.0864

GnomAD4 genome AF: 0.0625 AC: 9522 AN: 152236 Hom.: 456 Cov.: 31 AF XY: 0.0582 AC XY: 4332 AN XY: 74434

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0380

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0842

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0465

Alfa AF: 0.0906 Hom.: 1525

Bravo AF: 0.0571

TwinsUK AF: 0.126 AC: 468

ALSPAC AF: 0.125 AC: 483

ESP6500AA AF: 0.0222 AC: 67

ESP6500EA AF: 0.103 AC: 558

ExAC AF: 0.0596 AC: 7042

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.0930

EpiControl AF: 0.0865

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.4
DANN	Benign	0.95
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.39	T;.;T;T;T;T;T;T
MetaRNN	Benign	0.0020	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-2.0	N;N;N;N;.;N;N;.
REVEL	Benign	0.036
Sift	Uncertain	0.012	D;D;D;D;.;D;D;.
Sift4G	Benign	0.20	T;T;T;T;T;T;T;T
Vest4		0.15
MPC		1.1
ClinPred		0.029	T
GERP RS		-2.1
gMVP		0.031

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: rs7775397; hg19: chr6-32261252; COSMIC: COSV100898839;