16-3249586-G-C

Variant names:

• chr16-3249586-G-C
• NM_000243.3:c.1105C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000243.3(MEFV):​c.1105C>G​(p.Pro369Ala) 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. 14/21 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. P369S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MEFV NM_000243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16100132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEFV	NM_000243.3	c.1105C>G	p.Pro369Ala	missense_variant	Exon 3 of 10	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.472C>G	p.Pro158Ala	missense_variant	Exon 2 of 9		NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6	c.1105C>G	p.Pro369Ala	missense_variant	Exon 3 of 10	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.054	N
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.7	D;D;D;D
REVEL	Benign	0.15
Sift	Benign	0.12	T;T;D;T
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.98	D;.;.;.
Vest4		0.27
MutPred		0.26		Loss of glycosylation at P369 (P = 0.0402);.;.;.;
MVP		0.75
MPC		0.52
ClinPred		0.82	D
GERP RS		1.1
Varity_R		0.062
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr16-3299586;