rs104895103

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000243.3(MEFV):ā€‹c.322A>Gā€‹(p.Ser108Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. S108R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

MEFV
NM_000243.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.146
Variant links:
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]

Genome browser will be placed here

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=0.047293097).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MEFVNM_000243.3 linkuse as main transcriptc.322A>G p.Ser108Gly missense_variant 2/10 ENST00000219596.6
MEFVNM_001198536.2 linkuse as main transcriptc.277+1565A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MEFVENST00000219596.6 linkuse as main transcriptc.322A>G p.Ser108Gly missense_variant 2/101 NM_000243.3 P3O15553-2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000809
AC:
2
AN:
247174
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134744
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000180
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460468
Hom.:
0
Cov.:
64
AF XY:
0.00000138
AC XY:
1
AN XY:
726570
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
1.5
DANN
Benign
0.70
DEOGEN2
Benign
0.29
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.047
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.89
N
REVEL
Benign
0.046
Sift
Benign
0.55
T
Sift4G
Benign
0.55
T
Polyphen
0.0010
B
Vest4
0.10
MutPred
0.24
Loss of glycosylation at S108 (P = 0.012);
MVP
0.44
MPC
0.10
ClinPred
0.029
T
GERP RS
-1.4
Varity_R
0.042
gMVP
0.17

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs104895103; hg19: chr16-3304746; API