chr3-183193026-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015078.4(MCF2L2):​c.2989C>T​(p.Pro997Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MCF2L2
NM_015078.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.121
Variant links:
Genes affected
MCF2L2 (HGNC:30319): (MCF.2 cell line derived transforming sequence-like 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.043778688).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MCF2L2NM_015078.4 linkuse as main transcriptc.2989C>T p.Pro997Ser missense_variant 27/30 ENST00000328913.8
MCF2L2XM_011512585.3 linkuse as main transcriptc.1930C>T p.Pro644Ser missense_variant 19/22
MCF2L2XM_047447751.1 linkuse as main transcriptc.1888C>T p.Pro630Ser missense_variant 18/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MCF2L2ENST00000328913.8 linkuse as main transcriptc.2989C>T p.Pro997Ser missense_variant 27/305 NM_015078.4 A2Q86YR7-1
MCF2L2ENST00000473233.5 linkuse as main transcriptc.2989C>T p.Pro997Ser missense_variant 27/295 P4Q86YR7-4
MCF2L2ENST00000468976.5 linkuse as main transcriptn.370C>T non_coding_transcript_exon_variant 5/64
MCF2L2ENST00000488149.5 linkuse as main transcriptn.7436C>T non_coding_transcript_exon_variant 28/282

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461802
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727222
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 10, 2022The c.2989C>T (p.P997S) alteration is located in exon 27 (coding exon 27) of the MCF2L2 gene. This alteration results from a C to T substitution at nucleotide position 2989, causing the proline (P) at amino acid position 997 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
3.5
DANN
Benign
0.63
DEOGEN2
Benign
0.0016
T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.044
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.26
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.033
Sift
Benign
0.27
T;T
Sift4G
Benign
0.32
T;T
Polyphen
0.036
B;.
Vest4
0.076
MutPred
0.11
Gain of phosphorylation at P997 (P = 0.0202);Gain of phosphorylation at P997 (P = 0.0202);
MVP
0.067
MPC
0.19
ClinPred
0.052
T
GERP RS
2.0
Varity_R
0.060
gMVP
0.10

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: chr3-182910814; API