6-32293553-C-T

Variant names:

• chr6-32293553-C-T
• NM_001286474.2:c.1114G>A

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.1114G>A​(p.Gly372Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,722 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TSBP1 NM_001286474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.93
• Publications: 0 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=0.13176027).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSBP1	NM_001286474.2	MANE Select	c.1114G>A	p.Gly372Ser	missense	Exon 26 of 26	NP_001273403.1	A0A1U9X7D1
	TSBP1	NM_006781.5		c.1120G>A	p.Gly374Ser	missense	Exon 23 of 23	NP_006772.3
	TSBP1	NM_001286475.2		c.1072G>A	p.Gly358Ser	missense	Exon 24 of 24	NP_001273404.1	E9PLW3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSBP1	ENST00000533191.6	TSL:1 MANE Select	c.1114G>A	p.Gly372Ser	missense	Exon 26 of 26	ENSP00000431199.1	Q5SRN2-3
	TSBP1	ENST00000442822.6	TSL:1	c.1093G>A	p.Gly365Ser	missense	Exon 25 of 26	ENSP00000411164.2	C9J9T8
	TSBP1	ENST00000447241.6	TSL:5	c.1120G>A	p.Gly374Ser	missense	Exon 23 of 23	ENSP00000415517.2	Q5SRN2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460722 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726674

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.93
DANN	Uncertain	0.97
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.9
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.055
Sift	Benign	0.14	T
Sift4G	Benign	0.22	T
Vest4		0.15
MutPred		0.20		Gain of phosphorylation at G374 (P = 0.0135)
MVP		0.040
MPC		1.0
ClinPred		0.29	T
GERP RS		-0.21
gMVP		0.016
Mutation Taster		=100/0	polymorphism

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

hg19: chr6-32261330;