19-7916818-T-C

Variant names:

• chr19-7916818-T-C
• rs1983328239
• NM_001419781.1:c.401T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001419781.1(TGFBR3L):​c.401T>C​(p.Leu134Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000405 in 1,481,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: TGFBR3L NM_001419781.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0430
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

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.401T>C	p.Leu134Pro	missense	Exon 3 of 7	NP_001406710.1	H3BV60-1
	TGFBR3L	NM_001195259.2		c.473T>C	p.Leu158Pro	missense	Exon 2 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.401T>C	p.Leu134Pro	missense	Exon 3 of 7	ENSP00000519206.1	H3BV60-1
	TGFBR3L	ENST00000713908.1		c.401T>C	p.Leu134Pro	missense	Exon 3 of 6	ENSP00000519207.1	A0AAQ5BH11
	TGFBR3L	ENST00000869760.1		c.401T>C	p.Leu134Pro	missense	Exon 3 of 7	ENSP00000539819.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151754 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000376 AC: 5 AN: 1329300 Hom.: 0 Cov.: 31 AF XY: 0.00000458 AC XY: 3 AN XY: 655522

African (AFR) AF: 0.00 AC: 0 AN: 27046

American (AMR) AF: 0.00 AC: 0 AN: 30082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23414

East Asian (EAS) AF: 0.00 AC: 0 AN: 29650

South Asian (SAS) AF: 0.00 AC: 0 AN: 73984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4036

European-Non Finnish (NFE) AF: 0.00000380 AC: 4 AN: 1053016

Other (OTH) AF: 0.0000182 AC: 1 AN: 55038

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151754 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74116

African (AFR) AF: 0.00 AC: 0 AN: 41360

American (AMR) AF: 0.0000656 AC: 1 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10464

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67918

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Pathogenic	0.87	D
MutationAssessor	Benign	1.6	L
PhyloP100		-0.043
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-4.6	D
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.20	T
Vest4		0.78
MVP		0.92
GERP RS		2.9
Varity_R		0.86
gMVP		0.79
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs1983328239; hg19: chr19-7981703;