rs202110011

Variant names:

• chr16-31474232-C-G
• rs202110011
• NM_001042454.3:c.406C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-31474232-C-G
• chr16-31474232-C-T

Variant summary

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

The NM_001042454.3(TGFB1I1):​c.406C>G​(p.Pro136Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TGFB1I1 NM_001042454.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.358
• Publications: 2 publications found

Genes affected

TGFB1I1 (HGNC:11767): (transforming growth factor beta 1 induced transcript 1) This gene encodes a coactivator of the androgen receptor, a transcription factor which is activated by androgen and has a key role in male sexual differentiation. The encoded protein is thought to regulate androgen receptor activity and may have a role to play in the treatment of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

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=0.08796325).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042454.3. 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
	TGFB1I1	NM_001042454.3	MANE Select	c.406C>G	p.Pro136Ala	missense	Exon 5 of 11	NP_001035919.1	O43294-1
	TGFB1I1	NM_001164719.1		c.355C>G	p.Pro119Ala	missense	Exon 5 of 11	NP_001158191.1	O43294-2
	TGFB1I1	NM_015927.5		c.355C>G	p.Pro119Ala	missense	Exon 5 of 11	NP_057011.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFB1I1	ENST00000394863.8	TSL:1 MANE Select	c.406C>G	p.Pro136Ala	missense	Exon 5 of 11	ENSP00000378332.3	O43294-1
	TGFB1I1	ENST00000361773.7	TSL:1	c.355C>G	p.Pro119Ala	missense	Exon 5 of 11	ENSP00000355117.3	O43294-2
	TGFB1I1	ENST00000394858.6	TSL:1	c.355C>G	p.Pro119Ala	missense	Exon 5 of 11	ENSP00000378327.2	O43294-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.055
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.85
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.36
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.043
Sift	Benign	0.15	T
Sift4G	Benign	0.31	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.20		Loss of glycosylation at P136 (P = 0.023)
MVP		0.27
MPC		0.048
ClinPred		0.096	T
GERP RS		0.96
Varity_R		0.038
gMVP		0.35

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: rs202110011; hg19: chr16-31485553;