16-3247220-CC-TT

Variant names:

• chr16-3247220-CC-TT
• NM_000243.3:c.1382_1383delGGinsAA
• MEFV p.Arg461Gln

Variant summary

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

The NM_000243.3(MEFV):​c.1382_1383delGGinsAA​(p.Arg461Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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 benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R461P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MEFV NM_000243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.641
• 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 0 ACMG points.

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.1382_1383delGGinsAA	p.Arg461Gln	missense	N/A	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.749_750delGGinsAA	p.Arg250Gln	missense	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.1382_1383delGGinsAA	p.Arg461Gln	missense	N/A	ENSP00000219596.1	O15553-2
	MEFV	ENST00000541159.5	TSL:1	c.749_750delGGinsAA	p.Arg250Gln	missense	N/A	ENSP00000438711.1	O15553-3
	MEFV	ENST00000539145.5	TSL:1	n.*15_*16delGGinsAA		non_coding_transcript_exon	Exon 2 of 7	ENSP00000444471.1	D2DTW1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.64

Splicing

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: chr16-3297220;