6-32335915-T-C

Position:

• chr6-32335915-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/18 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: 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

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 Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSBP1	NM_001286474.2	c.400A>G	p.Ile134Val	missense_variant	14/26	ENST00000533191.6	NP_001273403.1
TSBP1-AS1	NR_136245.1	n.243-29865T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSBP1	ENST00000533191.6	c.400A>G	p.Ile134Val	missense_variant	14/26	1	NM_001286474.2	ENSP00000431199	A2
TSBP1-AS1	ENST00000645134.1	n.88-54299T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;T;T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.87	N;N;N;N;N;N
PROVEAN	Benign	-0.45	N;N;N;N;.;N;N
REVEL	Benign	0.044
Sift	Benign	0.049	D;D;T;D;.;D;D
Sift4G	Benign	0.25	T;T;T;T;T;T;T
Vest4		0.39
MutPred		0.098		.;Loss of ubiquitination at K155 (P = 0.1223);.;.;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1265754; hg19: chr6-32303692;