Variant 4-143611287-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001168235.2(FREM3):c.6020G>A(p.Arg2007His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,383,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

FREM3
NM_001168235.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.89

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07890001).

BP6

Variant 4-143611287-C-T is Benign according to our data. Variant chr4-143611287-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3279822.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FREM3	NM_001168235.2 linkuse as main transcript	c.6020G>A	p.Arg2007His	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.6020G>A	p.Arg2007His	missense_variant	6/8	5	NM_001168235.2	ENSP00000332886.5	P0C091
FREM3	ENST00000508899.1 linkuse as main transcript	n.257G>A		non_coding_transcript_exon_variant	2/3	5
ENSG00000251600	ENST00000511042.5 linkuse as main transcript	n.192-33798C>T		intron_variant		5
ENSG00000251600	ENST00000641328.1 linkuse as main transcript	n.861+38706C>T		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1383816

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

682742

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0030

DANN

Benign

0.76

DEOGEN2

Benign

0.0040

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.093

M_CAP

Benign

0.011

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.77

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.60

REVEL

Benign

0.023

Sift

Benign

0.17

Sift4G

Benign

0.21

Vest4

0.099

MutPred

0.35

Gain of glycosylation at Y2008 (P = 0.0101);

MVP

0.088

ClinPred

0.078

GERP RS

-8.2

Varity_R

0.016

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over