19-7917707-C-T

Variant names:

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

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>T​(p.Pro220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P220R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TGFBR3L NM_001419781.1 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.17803404).

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>T	p.Pro220Leu	missense	Exon 5 of 7	NP_001406710.1	H3BV60-1
	TGFBR3L	NM_001195259.2		c.731C>T	p.Pro244Leu	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>T	p.Pro220Leu	missense	Exon 5 of 7	ENSP00000519206.1	H3BV60-1
	TGFBR3L	ENST00000713908.1		c.760C>T	p.Pro254Ser	missense	Exon 4 of 6	ENSP00000519207.1	A0AAQ5BH11
	TGFBR3L	ENST00000869760.1		c.659C>T	p.Pro220Leu	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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1272962 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 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: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.18	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.25
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.4	D
Sift	Benign	0.16	T
Sift4G	Uncertain	0.0090	D
Vest4		0.13
MVP		0.83
GERP RS		3.1
Varity_R		0.12
gMVP		0.50
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;