rs7775397

Variant names:

• chr6-32293475-T-G
• rs7775397
• NM_001286474.2:c.1192A>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.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. 13/18 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 (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
• Publications: 73 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=0.0019672513).
• 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.1192A>C	p.Lys398Gln	missense	Exon 26 of 26	NP_001273403.1
	TSBP1	NM_006781.5		c.1198A>C	p.Lys400Gln	missense	Exon 23 of 23	NP_006772.3
	TSBP1	NM_001286475.2		c.1150A>C	p.Lys384Gln	missense	Exon 24 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.1192A>C	p.Lys398Gln	missense	Exon 26 of 26	ENSP00000431199.1
	TSBP1	ENST00000442822.6	TSL:1	c.1171A>C	p.Lys391Gln	missense	Exon 25 of 26	ENSP00000411164.2
	TSBP1	ENST00000447241.6	TSL:5	c.1198A>C	p.Lys400Gln	missense	Exon 23 of 23	ENSP00000415517.2

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

GnomAD2 exomes AF: 0.0595 AC: 14684 AN: 246618 AF XY: 0.0587

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 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

African (AFR) AF: 0.0158 AC: 528 AN: 33480

American (AMR) AF: 0.0226 AC: 1009 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0397 AC: 1038 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39694

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86256

European-Finnish (FIN) AF: 0.0857 AC: 4488 AN: 52348

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5768

European-Non Finnish (NFE) AF: 0.121 AC: 134568 AN: 1111944

Other (OTH) AF: 0.0864 AC: 5220 AN: 60386

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

African (AFR) AF: 0.0164 AC: 682 AN: 41552

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

Ashkenazi Jewish (ASJ) AF: 0.0380 AC: 132 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.0842 AC: 892 AN: 10598

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

European-Non Finnish (NFE) AF: 0.106 AC: 7222 AN: 67994

Other (OTH) AF: 0.0465 AC: 98 AN: 2106

Alfa AF: 0.0881 Hom.: 2934

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 v4.9

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
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.27
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.036
Sift	Uncertain	0.012	D
Sift4G	Benign	0.20	T
Vest4		0.15
MPC		1.1
ClinPred		0.029	T
GERP RS		-2.1
gMVP		0.031
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: rs7775397; hg19: chr6-32261252; COSMIC: COSV100898839;