MEFV p.Glu167Asp

Variant names:

• chr16-3254567-C-A
• NM_000243.3:c.501G>T
• MEFV p.Glu167Asp

Your query was ambiguous. Multiple possible variants found:

• chr16-3254567-C-A
• chr16-3254567-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PS1_Moderate PM2

The NM_000243.3(MEFV):​c.501G>T​(p.Glu167Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar. Synonymous variant affecting the same amino acid position (i.e. E167E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEFV NM_000243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• 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, SD, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Myriad Women’s Health, ClinGen, Orphanet
• familial Mediterranean fever, autosomal dominant

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PS1: Transcript NM_000243.3 (MEFV) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PM2: Very rare variant in population databases, with high coverage

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.501G>T	p.Glu167Asp	missense	Exon 2 of 10	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.277+1744G>T		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.501G>T	p.Glu167Asp	missense	Exon 2 of 10	ENSP00000219596.1	O15553-2
	MEFV	ENST00000541159.5	TSL:1	c.277+1744G>T		intron	N/A	ENSP00000438711.1	O15553-3
	MEFV	ENST00000570511.5	TSL:1	n.501G>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000458312.1	I3L0S7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1419548 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 703922

African (AFR) AF: 0.00 AC: 0 AN: 32598

American (AMR) AF: 0.00 AC: 0 AN: 38964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25470

East Asian (EAS) AF: 0.00 AC: 0 AN: 37738

South Asian (SAS) AF: 0.00 AC: 0 AN: 83368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4966

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094644

Other (OTH) AF: 0.00 AC: 0 AN: 58828

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.30
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.54
Sift	Uncertain	0.014	D
Sift4G	Benign	0.17	T
Varity_R		0.14
gMVP		0.38

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

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

Other links and lift over

hg19: chr16-3304567;