chr3-183179656-T-A

Position:

• chr3-183179656-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015078.4(MCF2L2):​c.3142A>T​(p.Thr1048Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1048I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCF2L2 NM_015078.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0450

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]

ACMG classification

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=0.03662139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2L2	NM_015078.4	c.3142A>T	p.Thr1048Ser	missense_variant	29/30	ENST00000328913.8
MCF2L2	XM_011512585.3	c.2083A>T	p.Thr695Ser	missense_variant	21/22
MCF2L2	XM_047447751.1	c.2041A>T	p.Thr681Ser	missense_variant	20/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2L2	ENST00000328913.8	c.3142A>T	p.Thr1048Ser	missense_variant	29/30	5	NM_015078.4	A2
MCF2L2	ENST00000473233.5	c.3142A>T	p.Thr1048Ser	missense_variant	29/29	5		P4
MCF2L2	ENST00000464626.1	n.278A>T		non_coding_transcript_exon_variant	2/2	4
MCF2L2	ENST00000478652.1	n.280A>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.3142A>T (p.T1048S) alteration is located in exon 29 (coding exon 29) of the MCF2L2 gene. This alteration results from a A to T substitution at nucleotide position 3142, causing the threonine (T) at amino acid position 1048 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	0.083
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.61
DEOGEN2	Benign	0.00033	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.28	T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.97	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.53	N;N
REVEL	Benign	0.025
Sift	Benign	0.039	D;T
Sift4G	Benign	0.85	T;T
Polyphen		0.0050	B;.
Vest4		0.11
MutPred		0.15		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.061
MPC		0.16
ClinPred		0.042	T
GERP RS		-1.6
Varity_R		0.035
gMVP		0.086

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: chr3-182897444;