6-32335915-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286474.2(TSBP1):​c.400A>G​(p.Ile134Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15200427).

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>G	p.Ile134Val	missense	Exon 14 of 26	NP_001273403.1
	TSBP1	NM_006781.5		c.448A>G	p.Ile150Val	missense	Exon 13 of 23	NP_006772.3
	TSBP1	NM_001286475.2		c.379A>G	p.Ile127Val	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>G	p.Ile134Val	missense	Exon 14 of 26	ENSP00000431199.1
	TSBP1	ENST00000442822.6	TSL:1	c.379A>G	p.Ile127Val	missense	Exon 13 of 26	ENSP00000411164.2
	TSBP1	ENST00000447241.6	TSL:5	c.448A>G	p.Ile150Val	missense	Exon 13 of 23	ENSP00000415517.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456220 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724788

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108688

Other (OTH) AF: 0.00 AC: 0 AN: 60230

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 447

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.060
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.96
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.044
Sift	Benign	0.049	D
Sift4G	Benign	0.25	T
Vest4		0.39
MutPred		0.098		Loss of ubiquitination at K155 (P = 0.1223)
MVP		0.048
MPC		0.26
ClinPred		0.17	T
GERP RS		3.0
gMVP		0.021
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;