NM_001168235.2:c.6080G>C

Variant names:

• chr4-143585942-C-G
• rs373667244
• NM_001168235.2:c.6080G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001168235.2(FREM3):​c.6080G>C​(p.Arg2027Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. R2027H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FREM3 NM_001168235.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• Publications: 0 publications found

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]

GUSBP5 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18448898).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168235.2. 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
	FREM3	NM_001168235.2	MANE Select	c.6080G>C	p.Arg2027Pro	missense	Exon 7 of 8	NP_001161707.1	P0C091

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FREM3	ENST00000329798.5	TSL:5 MANE Select	c.6080G>C	p.Arg2027Pro	missense	Exon 7 of 8	ENSP00000332886.5	P0C091
	GUSBP5	ENST00000511042.5	TSL:5	n.191+13361C>G		intron	N/A
	GUSBP5	ENST00000641328.2		n.862+13361C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.024
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.55	N
PhyloP100		3.8
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.070
Sift	Benign	0.053	T
Sift4G	Benign	0.091	T
Vest4		0.29
MutPred		0.58		Loss of stability (P = 0.0204)
MVP		0.067
ClinPred		0.82	D
GERP RS		4.4
Varity_R		0.24
gMVP		0.88
Mutation Taster		=69/31	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: rs373667244; hg19: chr4-144507095;