MEFV p.Asn99Lys

Variant names:

• chr16-3254771-G-T
• NM_000243.3:c.297C>A
• MEFV p.Asn99Lys

Your query was ambiguous. Multiple possible variants found:

• chr16-3254771-G-T
• chr16-3254771-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000243.3(MEFV):​c.297C>A​(p.Asn99Lys) 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. Synonymous variant affecting the same amino acid position (i.e. N99N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEFV NM_000243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• 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):

• autosomal recessive familial Mediterranean fever

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

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06464225).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	NM_000243.3	MANE Select	c.297C>A	p.Asn99Lys	missense	Exon 2 of 10	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.277+1540C>A		intron	N/A	NP_001185465.2	O15553-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.297C>A	p.Asn99Lys	missense	Exon 2 of 10	ENSP00000219596.1	O15553-2
	MEFV	ENST00000541159.5	TSL:1	c.277+1540C>A		intron	N/A	ENSP00000438711.1	O15553-3
	MEFV	ENST00000570511.5	TSL:1	n.297C>A		non_coding_transcript_exon	Exon 2 of 6	ENSP00000458312.1	I3L0S7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.085
DANN	Benign	0.76
DEOGEN2	Benign	0.32	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.60
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Benign	0.077	T
Sift4G	Benign	0.15	T
Varity_R		0.053
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-3304771;