chr16-3242361-C-CAA

Variant names:

• chr16-3242361-C-CAA
• rs60407399
• NM_000243.3:c.*778_*779dupTT

Variant summary

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

The NM_000243.3(MEFV):​c.*778_*779dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 73,276 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0042 (0 hom.)
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• 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.*778_*779dupTT		3_prime_UTR	Exon 10 of 10	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.*1328_*1329dupTT		3_prime_UTR	Exon 9 of 9	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.*778_*779dupTT		3_prime_UTR	Exon 10 of 10	ENSP00000219596.1	O15553-2
	MEFV	ENST00000956137.1		c.*778_*779dupTT		3_prime_UTR	Exon 10 of 10	ENSP00000626196.1
	MEFV	ENST00000339854.8	TSL:5	c.*778_*779dupTT		3_prime_UTR	Exon 10 of 10	ENSP00000339639.4	F8W6Z2

Frequencies

GnomAD3 genomes AF: 0.000137 AC: 10 AN: 73030 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000951

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000476

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000202

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00424 AC: 1 AN: 236 Hom.: 0 Cov.: 0 AF XY: 0.00602 AC XY: 1 AN XY: 166

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0119 AC: 1 AN: 84

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000137 AC: 10 AN: 73040 Hom.: 0 Cov.: 22 AF XY: 0.000117 AC XY: 4 AN XY: 34208

African (AFR) AF: 0.0000950 AC: 2 AN: 21046

American (AMR) AF: 0.00 AC: 0 AN: 6102

Ashkenazi Jewish (ASJ) AF: 0.000476 AC: 1 AN: 2100

East Asian (EAS) AF: 0.00 AC: 0 AN: 2852

South Asian (SAS) AF: 0.00 AC: 0 AN: 2304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 80

European-Non Finnish (NFE) AF: 0.000202 AC: 7 AN: 34666

Other (OTH) AF: 0.00 AC: 0 AN: 926

Alfa AF: 0.00 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32

Splicing

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

Other links and lift over

dbSNP: rs60407399; hg19: chr16-3292361;