16-31473506-C-A

Position:

• chr16-31473506-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001042454.3(TGFB1I1):​c.79C>A​(p.Arg27Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TGFB1I1 NM_001042454.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

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]

TGFB1I1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.076747954).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFB1I1	NM_001042454.3	c.79C>A	p.Arg27Ser	missense_variant	2/11	ENST00000394863.8	NP_001035919.1
TGFB1I1	NM_001164719.1	c.28C>A	p.Arg10Ser	missense_variant	2/11		NP_001158191.1
TGFB1I1	NM_015927.5	c.28C>A	p.Arg10Ser	missense_variant	2/11		NP_057011.2
TGFB1I1	XM_024450412.2	c.28C>A	p.Arg10Ser	missense_variant	2/11		XP_024306180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFB1I1	ENST00000394863.8	c.79C>A	p.Arg27Ser	missense_variant	2/11	1	NM_001042454.3	ENSP00000378332.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461520 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727108

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: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2022

The c.79C>A (p.R27S) alteration is located in exon 2 (coding exon 2) of the TGFB1I1 gene. This alteration results from a C to A substitution at nucleotide position 79, causing the arginine (R) at amino acid position 27 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.78
DEOGEN2	Benign	0.0082	T;T;.;.;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T;T;T;T;.;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.077	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L;.;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.070	N;N;N;N;N;N
REVEL	Benign	0.049
Sift	Uncertain	0.0040	D;T;D;D;D;D
Sift4G	Benign	0.17	T;T;T;T;T;T
Polyphen		0.0070	.;B;.;.;.;.
Vest4		0.34, 0.37, 0.38, 0.38
MutPred		0.20		.;Gain of phosphorylation at R27 (P = 0.007);.;.;.;.;
MVP		0.36
MPC		0.073
ClinPred		0.31	T
GERP RS		2.5
Varity_R		0.075
gMVP		0.20

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-31484827;