16-3249562-G-C

Position:

• chr16-3249562-G-C

Variant summary

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

The NM_000243.3(MEFV):​c.1129C>G​(p.Arg377Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MEFV NM_000243.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.105

Genes affected

MEFV (HGNC:6998): (MEFV innate immunity regulator, pyrin) This gene encodes a protein, also known as pyrin or marenostrin, that is an important modulator of innate immunity. Mutations in this gene are associated with Mediterranean fever, a hereditary periodic fever syndrome. [provided by RefSeq, Jul 2008]

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=0.3427591).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEFV	NM_000243.3	c.1129C>G	p.Arg377Gly	missense_variant	3/10	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.496C>G	p.Arg166Gly	missense_variant	2/9		NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6	c.1129C>G	p.Arg377Gly	missense_variant	3/10	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial Mediterranean fever Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals

Jul 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.;.;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.070
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.8	M;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.0	D;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.019	D;D;D;D
Sift4G	Uncertain	0.041	D;T;D;T
Polyphen		0.72	P;.;.;.
Vest4		0.35
MutPred		0.44		Gain of ubiquitination at K376 (P = 0.0304);.;.;.;
MVP		0.71
MPC		0.59
ClinPred		0.95	D
GERP RS		4.4
Varity_R		0.28
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs896909303; hg19: chr16-3299562;