TGFB1I1 p.Ser61Arg

Variant names:

• chr16-31473733-A-C
• NM_001042454.3:c.181A>C
• TGFB1I1 p.Ser61Arg

Your query was ambiguous. Multiple possible variants found:

• chr16-31473733-A-C
• chr16-31473735-C-A
• chr16-31473735-C-G
• chr16-31473733-AGC-CGT
• chr16-31473733-AGC-CGA
• chr16-31473733-AGC-CGG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001042454.3(TGFB1I1):​c.181A>C​(p.Ser61Arg) variant causes a missense, splice region 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. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TGFB1I1 NM_001042454.3 missense, splice_region
• Scores: Splicing: ADA: 0.9942
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.01
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

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.181A>C	p.Ser61Arg	missense splice_region	Exon 3 of 11	NP_001035919.1	O43294-1
	TGFB1I1	NM_001164719.1		c.130A>C	p.Ser44Arg	missense splice_region	Exon 3 of 11	NP_001158191.1	O43294-2
	TGFB1I1	NM_015927.5		c.130A>C	p.Ser44Arg	missense splice_region	Exon 3 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.181A>C	p.Ser61Arg	missense splice_region	Exon 3 of 11	ENSP00000378332.3	O43294-1
	TGFB1I1	ENST00000361773.7	TSL:1	c.130A>C	p.Ser44Arg	missense splice_region	Exon 3 of 11	ENSP00000355117.3	O43294-2
	TGFB1I1	ENST00000394858.6	TSL:1	c.130A>C	p.Ser44Arg	missense splice_region	Exon 3 of 11	ENSP00000378327.2	O43294-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.019
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.14	T
PromoterAI		-0.0082	Neutral
Varity_R		0.68
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.81
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.31		Position offset: 46
DS_DL_spliceai		0.44		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-31485054;