Variant rs72938299 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001168235.2(FREM3):c.5816T>C(p.Phe1939Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,537,030 control chromosomes in the GnomAD database, including 957 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.048 ( 465 hom., cov: 33)

Exomes 𝑓: 0.0094 ( 492 hom. )

Consequence

FREM3
NM_001168235.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.30

Variant links:

Genes affected

FREM3 (HGNC:25172): (FRAS1 related extracellular matrix 3) This gene encodes an integral membrane protein containing numerous CSPG (chondroitin sulfate proteoglycan element) repeats and Calx-beta domains. The protein belongs to the family of FRAS1/FREM extracellular matrix proteins and may play a role cell adhesion. [provided by RefSeq, Feb 2017]

FREM3 links:

FREM3 (HGNC:):

FREM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016269386).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FREM3	NM_001168235.2 linkuse as main transcript	c.5816T>C	p.Phe1939Ser	missense_variant	6/8	ENST00000329798.5	NP_001161707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FREM3	ENST00000329798.5 linkuse as main transcript	c.5816T>C	p.Phe1939Ser	missense_variant	6/8	5	NM_001168235.2	ENSP00000332886.5	P0C091
FREM3	ENST00000508899.1 linkuse as main transcript	n.53T>C		non_coding_transcript_exon_variant	2/3	5
ENSG00000251600	ENST00000511042.5 linkuse as main transcript	n.192-33594A>G		intron_variant		5
ENSG00000251600	ENST00000641328.1 linkuse as main transcript	n.861+38910A>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7258

AN:

152170

Hom.:

465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0241

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.0591

Gnomad SAS

AF:

0.00848

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00426

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0190

AC:

2699

AN:

141946

Hom.:

108

AF XY:

0.0163

AC XY:

1242

AN XY:

76004

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.0142

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.0539

Gnomad SAS exome

AF:

0.00541

Gnomad FIN exome

AF:

0.000432

Gnomad NFE exome

AF:

0.00503

Gnomad OTH exome

AF:

0.0172

GnomAD4 exome

AF:

0.00938

AC:

12984

AN:

1384742

Hom.:

492

Cov.:

AF XY:

0.00895

AC XY:

6114

AN XY:

683304

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.0141

Gnomad4 EAS exome

AF:

0.0372

Gnomad4 SAS exome

AF:

0.00627

Gnomad4 FIN exome

AF:

0.000686

Gnomad4 NFE exome

AF:

0.00370

Gnomad4 OTH exome

AF:

0.0209

GnomAD4 genome

AF:

0.0477

AC:

7270

AN:

152288

Hom.:

465

Cov.:

AF XY:

0.0466

AC XY:

3470

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.0241

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.0587

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00426

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0550

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.149

AC:

206

ESP6500EA

AF:

0.00503

AC:

ExAC

AF:

0.0187

AC:

439

Asia WGS

AF:

0.0510

AC:

177

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0013

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.37

PROVEAN

Benign

0.050

REVEL

Benign

0.065

Sift

Uncertain

0.014

Sift4G

Uncertain

0.0040

Vest4

0.045

ClinPred

0.039

GERP RS

1.4

Varity_R

0.13

gMVP

0.91

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over