rs1249854544

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001112732.3(MCF2L):​c.586C>G​(p.Arg196Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,378 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R196Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

MCF2L
NM_001112732.3 missense

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.06
Variant links:
Genes affected
MCF2L (HGNC:14576): (MCF.2 cell line derived transforming sequence like) This gene encodes a guanine nucleotide exchange factor that interacts specifically with the GTP-bound Rac1 and plays a role in the Rho/Rac signaling pathways. A variant in this gene was associated with osteoarthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MCF2LNM_001112732.3 linkc.586C>G p.Arg196Gly missense_variant Exon 6 of 30 ENST00000535094.7 NP_001106203.2 O15068-9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MCF2LENST00000535094.7 linkc.586C>G p.Arg196Gly missense_variant Exon 6 of 30 2 NM_001112732.3 ENSP00000440374.2 O15068-9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459378
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726078
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T;.;.;.;.;.;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.44
N
LIST_S2
Uncertain
0.91
D;D;D;D;D;D;D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.43
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;.;.;.;.;.;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.7
D;D;D;D;D;D;D
REVEL
Benign
0.15
Sift
Benign
0.044
D;T;T;T;D;T;T
Sift4G
Uncertain
0.045
D;D;D;D;D;D;T
Polyphen
0.27
B;.;B;.;.;B;.
Vest4
0.69
MVP
0.88
MPC
0.57
ClinPred
0.98
D
GERP RS
1.2
Varity_R
0.23
gMVP
0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-113718714; API