rs104895198

Variant names:

• chr16-3249648-C-G
• rs104895198
• NM_000243.3:c.1043G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-3249648-C-G
• chr16-3249648-C-T

Variant summary

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

The NM_000243.3(MEFV):​c.1043G>C​(p.Arg348Pro) 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. 17/22 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. R348H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MEFV NM_000243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91
• Publications: 0 publications found

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]

MEFV Gene-Disease associations (from GenCC):

• familial Mediterranean fever

  Inheritance: AD, AR, SD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, ClinGen
• autosomal recessive familial Mediterranean fever

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• familial Mediterranean fever, autosomal dominant

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

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=0.11870912).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000243.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	NM_000243.3	MANE Select	c.1043G>C	p.Arg348Pro	missense	Exon 3 of 10	NP_000234.1
	MEFV	NM_001198536.2		c.410G>C	p.Arg137Pro	missense	Exon 2 of 9	NP_001185465.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.1043G>C	p.Arg348Pro	missense	Exon 3 of 10	ENSP00000219596.1
	MEFV	ENST00000541159.5	TSL:1	c.410G>C	p.Arg137Pro	missense	Exon 2 of 9	ENSP00000438711.1
	MEFV	ENST00000539145.5	TSL:1	n.278-2402G>C		intron	N/A	ENSP00000444471.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.12
DANN	Benign	0.90
DEOGEN2	Benign	0.31	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PhyloP100		-2.9
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Benign	0.18	T
Sift4G	Benign	0.21	T
Polyphen		0.34	B
Vest4		0.15
MutPred		0.26		Gain of glycosylation at R348 (P = 0.0264)
MVP		0.34
MPC		0.17
ClinPred		0.36	T
GERP RS		-8.2
Varity_R		0.13
gMVP		0.27

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: rs104895198; hg19: chr16-3299648;