16-31473507-G-C

Variant names:

• chr16-31473507-G-C
• rs769255371
• NM_001042454.3:c.80G>C

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.80G>C​(p.Arg27Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R27S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TGFB1I1 NM_001042454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08486611).

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.80G>C	p.Arg27Pro	missense	Exon 2 of 11	NP_001035919.1	O43294-1
	TGFB1I1	NM_001164719.1		c.29G>C	p.Arg10Pro	missense	Exon 2 of 11	NP_001158191.1	O43294-2
	TGFB1I1	NM_015927.5		c.29G>C	p.Arg10Pro	missense	Exon 2 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.80G>C	p.Arg27Pro	missense	Exon 2 of 11	ENSP00000378332.3	O43294-1
	TGFB1I1	ENST00000361773.7	TSL:1	c.29G>C	p.Arg10Pro	missense	Exon 2 of 11	ENSP00000355117.3	O43294-2
	TGFB1I1	ENST00000394858.6	TSL:1	c.29G>C	p.Arg10Pro	missense	Exon 2 of 11	ENSP00000378327.2	O43294-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461516 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727086

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53066

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Benign	0.77
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.085	T
PhyloP100		0.53
PROVEAN	Benign	0.41	N
Sift	Benign	0.12	T
Sift4G	Benign	0.29	T
MVP		0.12
ClinPred		0.36	T
GERP RS		1.3
PromoterAI		0.062	Neutral
Varity_R		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs769255371; hg19: chr16-31484828;