chr4-143585880-C-A

Variant names:

• chr4-143585880-C-A
• NM_001168235.2:c.6142G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001168235.2(FREM3):​c.6142G>T​(p.Val2048Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,998 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FREM3 NM_001168235.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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]

ENSG00000251600 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29945666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FREM3	NM_001168235.2	c.6142G>T	p.Val2048Leu	missense_variant	Exon 7 of 8	ENST00000329798.5	NP_001161707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FREM3	ENST00000329798.5	c.6142G>T	p.Val2048Leu	missense_variant	Exon 7 of 8	5	NM_001168235.2	ENSP00000332886.5
ENSG00000251600	ENST00000511042.5	n.191+13299C>A		intron_variant	Intron 2 of 3	5
ENSG00000251600	ENST00000641328.1	n.861+13299C>A		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1384998 Hom.: 0 Cov.: 31 AF XY: 0.00000293 AC XY: 2 AN XY: 683424

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: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.0
DANN	Benign	0.89
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.075
Sift	Benign	0.044	D
Sift4G	Benign	0.066	T
Vest4		0.16
MutPred		0.70		Gain of glycosylation at S2053 (P = 0.0028);
MVP		0.28
ClinPred		0.13	T
GERP RS		0.46
Varity_R		0.091
gMVP		0.65

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-144507033;