Variant chr3-183179655-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015078.4(MCF2L2):c.3143C>T(p.Thr1048Ile) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1048S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MCF2L2
NM_015078.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

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]

MCF2L2 links:

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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=0.05072269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MCF2L2	NM_015078.4 linkuse as main transcript	c.3143C>T	p.Thr1048Ile	missense_variant	29/30	ENST00000328913.8
MCF2L2	XM_011512585.3 linkuse as main transcript	c.2084C>T	p.Thr695Ile	missense_variant	21/22
MCF2L2	XM_047447751.1 linkuse as main transcript	c.2042C>T	p.Thr681Ile	missense_variant	20/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2L2	ENST00000328913.8 linkuse as main transcript	c.3143C>T	p.Thr1048Ile	missense_variant	29/30	5	NM_015078.4	A2	Q86YR7-1
MCF2L2	ENST00000473233.5 linkuse as main transcript	c.3143C>T	p.Thr1048Ile	missense_variant	29/29	5		P4	Q86YR7-4
MCF2L2	ENST00000464626.1 linkuse as main transcript	n.279C>T		non_coding_transcript_exon_variant	2/2	4
MCF2L2	ENST00000478652.1 linkuse as main transcript	n.281C>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727204

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.:

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 submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.3143C>T (p.T1048I) alteration is located in exon 29 (coding exon 29) of the MCF2L2 gene. This alteration results from a C to T substitution at nucleotide position 3143, causing the threonine (T) at amino acid position 1048 to be replaced by an isoleucine (I). 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

0.098

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.00085

T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.88

N;N

REVEL

Benign

0.023

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.13

T;T

Polyphen

0.0030

B;.

Vest4

0.14

MutPred

0.20

Loss of phosphorylation at T1048 (P = 0.0143);Loss of phosphorylation at T1048 (P = 0.0143);

MVP

0.13

MPC

0.32

ClinPred

0.11

GERP RS

2.2

Varity_R

0.087

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over