19-41353016-G-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_000660.7(TGFB1):āc.29C>Gā(p.Pro10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000988 in 1,528,168 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P10L) has been classified as Benign.
Frequency
Consequence
NM_000660.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFB1 | NM_000660.7 | c.29C>G | p.Pro10Arg | missense_variant | 1/7 | ENST00000221930.6 | |
TGFB1 | XM_011527242.3 | c.29C>G | p.Pro10Arg | missense_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFB1 | ENST00000221930.6 | c.29C>G | p.Pro10Arg | missense_variant | 1/7 | 1 | NM_000660.7 | P1 | |
TMEM91 | ENST00000539627.5 | c.-30+1814G>C | intron_variant | 1 | |||||
TGFB1 | ENST00000600196.2 | c.29C>G | p.Pro10Arg | missense_variant | 1/6 | 5 | |||
TGFB1 | ENST00000677934.1 | c.29C>G | p.Pro10Arg | missense_variant | 1/5 |
Frequencies
GnomAD3 genomes AF: 0.0000790 AC: 12AN: 151942Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000239 AC: 31AN: 129938Hom.: 0 AF XY: 0.000339 AC XY: 24AN XY: 70790
GnomAD4 exome AF: 0.000101 AC: 139AN: 1376108Hom.: 1 Cov.: 55 AF XY: 0.000150 AC XY: 102AN XY: 678550
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152060Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 17, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1473460). This variant has not been reported in the literature in individuals affected with TGFB1-related conditions. This variant is present in population databases (rs1800470, gnomAD 0.1%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 10 of the TGFB1 protein (p.Pro10Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at