19-7917597-C-G

Position:

chr19-7917597-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001195259.2(TGFBR3L):c.722C>G(p.Pro241Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,474,844 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 2 hom. )

Consequence

TGFBR3L
NM_001195259.2 missense, splice_region

Scores

Splicing: ADA: 0.03302

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0430

Variant links:

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]

TGFBR3L links:

TGFBR3L (HGNC:):

TGFBR3L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070527196).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3L	NM_001195259.2 linkuse as main transcript	c.722C>G	p.Pro241Arg	missense_variant, splice_region_variant	3/6	ENST00000565886.2	NP_001182188.1	H3BV60-2
TGFBR3L	XM_011527610.3 linkuse as main transcript	c.800C>G	p.Pro267Arg	missense_variant	2/4		XP_011525912.1
TGFBR3L	NM_001419781.1 linkuse as main transcript	c.650C>G	p.Pro217Arg	missense_variant, splice_region_variant	4/7		NP_001406710.1
TGFBR3L	XM_011527613.3 linkuse as main transcript	c.800C>G	p.Pro267Arg	missense_variant, splice_region_variant	2/5		XP_011525915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
TGFBR3L	ENST00000565886.2 linkuse as main transcript	c.722C>G	p.Pro241Arg	missense_variant, splice_region_variant	3/6	5	NM_001195259.2	H3BV60-2
TGFBR3L	ENST00000564348.5 linkuse as main transcript	n.220C>G		splice_region_variant, non_coding_transcript_exon_variant	2/5	5
TGFBR3L	ENST00000566166.1 linkuse as main transcript	n.-31C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000460

AC:

AN:

80442

Hom.:

AF XY:

0.000631

AC XY:

AN XY:

44400

show subpopulations

Gnomad AFR exome

AF:

0.000512

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00236

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000393

GnomAD4 exome

AF:

0.000144

AC:

190

AN:

1322482

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

134

AN XY:

647026

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.0000701

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00202

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.000236

GnomAD4 genome

AF:

0.000269

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000253

ExAC

AF:

0.000341

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2021

The c.722C>G (p.P241R) alteration is located in exon 3 (coding exon 3) of the TGFBR3L gene. This alteration results from a C to G substitution at nucleotide position 722, causing the proline (P) at amino acid position 241 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0071

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.1

Sift

Benign

0.15

Sift4G

Pathogenic

0.0

Vest4

0.31

MVP

0.71

GERP RS

3.0

Varity_R

0.041

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.033

dbscSNV1_RF

Benign

0.22

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over