Variant 16-3243588-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_000243.3(MEFV):c.1899G>A(p.Pro633=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 1,603,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P633P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

MEFV
NM_000243.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -2.79

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-3243588-C-T is Benign according to our data. Variant chr16-3243588-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 793936.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=-2.79 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEFV	NM_000243.3 linkuse as main transcript	c.1899G>A	p.Pro633=	synonymous_variant	10/10	ENST00000219596.6
MEFV	NM_001198536.2 linkuse as main transcript	c.*103G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEFV	ENST00000219596.6 linkuse as main transcript	c.1899G>A	p.Pro633=	synonymous_variant	10/10	1	NM_000243.3	P3	O15553-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000819

AC:

AN:

244164

Hom.:

AF XY:

0.00000758

AC XY:

AN XY:

131950

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000342

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000827

AC:

AN:

1450944

Hom.:

Cov.:

AF XY:

0.00000833

AC XY:

AN XY:

720646

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000352

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000814

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Familial Mediterranean fever

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Feb 08, 2023	- -
Likely benign, no assertion criteria provided	clinical testing	Natera, Inc.	Oct 24, 2020	- -

Acute febrile neutrophilic dermatosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Familial Mediterranean fever;C0085077:Acute febrile neutrophilic dermatosis;C1851347:Familial Mediterranean fever, autosomal dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 14, 2021

- -

Familial Mediterranean fever, autosomal dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.1

DANN

Benign

0.43

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over