19-7917707-C-G

Variant names:

• chr19-7917707-C-G
• rs547524116
• NM_001419781.1:c.659C>G

Variant summary

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

The NM_001419781.1(TGFBR3L):​c.659C>G​(p.Pro220Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,425,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: TGFBR3L NM_001419781.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.249
• Publications: 0 publications found

Genes affected

TGFBR3L (HGNC:44152): (transforming growth factor beta receptor 3 like) Predicted to enable glycosaminoglycan binding activity; transforming growth factor beta-activated receptor activity; and type II transforming growth factor beta receptor binding activity. Predicted to contribute to transforming growth factor beta binding activity. Predicted to be involved in several processes, including blood vessel morphogenesis; regulation of transforming growth factor beta receptor signaling pathway; and transforming growth factor beta receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be active in cell surface and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000294288 (HGNC:):

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=0.10872531).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001419781.1. 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
	TGFBR3L	NM_001419781.1	MANE Select	c.659C>G	p.Pro220Arg	missense	Exon 5 of 7	NP_001406710.1	H3BV60-1
	TGFBR3L	NM_001195259.2		c.731C>G	p.Pro244Arg	missense	Exon 4 of 6	NP_001182188.1	H3BV60-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3L	ENST00000713907.1	MANE Select	c.659C>G	p.Pro220Arg	missense	Exon 5 of 7	ENSP00000519206.1	H3BV60-1
	TGFBR3L	ENST00000713908.1		c.760C>G	p.Pro254Ala	missense	Exon 4 of 6	ENSP00000519207.1	A0AAQ5BH11
	TGFBR3L	ENST00000869760.1		c.659C>G	p.Pro220Arg	missense	Exon 5 of 7	ENSP00000539819.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000314 AC: 4 AN: 1272962 Hom.: 0 Cov.: 32 AF XY: 0.00000645 AC XY: 4 AN XY: 620424

African (AFR) AF: 0.00 AC: 0 AN: 25202

American (AMR) AF: 0.00 AC: 0 AN: 18440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19504

East Asian (EAS) AF: 0.00 AC: 0 AN: 29168

South Asian (SAS) AF: 0.0000624 AC: 4 AN: 64116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029126

Other (OTH) AF: 0.00 AC: 0 AN: 52774

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152352 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74498

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.11	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.25
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	D
Sift	Benign	0.13	T
Sift4G	Uncertain	0.0080	D
Vest4		0.13
MVP		0.72
GERP RS		3.1
Varity_R		0.15
gMVP		0.48
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs547524116; hg19: chr19-7982592;