19-7916643-C-T

Variant names:

• chr19-7916643-C-T
• rs1368045650
• NM_001419781.1:c.226C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001419781.1(TGFBR3L):​c.226C>T​(p.Pro76Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,270,222 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. P76A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: TGFBR3L NM_001419781.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26791123).

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.226C>T	p.Pro76Ser	missense	Exon 3 of 7	NP_001406710.1	H3BV60-1
	TGFBR3L	NM_001195259.2		c.298C>T	p.Pro100Ser	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.226C>T	p.Pro76Ser	missense	Exon 3 of 7	ENSP00000519206.1	H3BV60-1
	TGFBR3L	ENST00000713908.1		c.226C>T	p.Pro76Ser	missense	Exon 3 of 6	ENSP00000519207.1	A0AAQ5BH11
	TGFBR3L	ENST00000869760.1		c.226C>T	p.Pro76Ser	missense	Exon 3 of 7	ENSP00000539819.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000157 AC: 2 AN: 1270222 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 619118

African (AFR) AF: 0.00 AC: 0 AN: 24548

American (AMR) AF: 0.00 AC: 0 AN: 17158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18022

East Asian (EAS) AF: 0.00 AC: 0 AN: 31194

South Asian (SAS) AF: 0.00 AC: 0 AN: 61028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3708

European-Non Finnish (NFE) AF: 0.00000194 AC: 2 AN: 1031748

Other (OTH) AF: 0.00 AC: 0 AN: 52722

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.27	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.42
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.0	D
Sift	Benign	0.15	T
Sift4G	Benign	0.085	T
Vest4		0.10
MVP		0.84
GERP RS		2.8
Varity_R		0.11
gMVP		0.24
Mutation Taster		=89/11	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: rs1368045650; hg19: chr19-7981528;