NM_001112732.3:c.46G>C

Variant names:

• chr13-112969425-G-C
• NM_001112732.3:c.46G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001112732.3(MCF2L):​c.46G>C​(p.Val16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 7.2e-7 (0 hom.)
• Consequence: MCF2L NM_001112732.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29
• Publications: 0 publications found

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]

ENSG00000289354 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10178232).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001112732.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2L	NM_001112732.3	MANE Select	c.46G>C	p.Val16Leu	missense	Exon 1 of 30	NP_001106203.2	O15068-9
	MCF2L	NM_001438761.1		c.-92G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 32	NP_001425690.1
	MCF2L	NM_001437889.1		c.46G>C	p.Val16Leu	missense	Exon 1 of 32	NP_001424818.1	H0Y4M6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2L	ENST00000535094.7	TSL:2 MANE Select	c.46G>C	p.Val16Leu	missense	Exon 1 of 30	ENSP00000440374.2	O15068-9
	MCF2L	ENST00000884942.1		c.46G>C	p.Val16Leu	missense	Exon 1 of 31	ENSP00000555001.1
	MCF2L	ENST00000884941.1		c.46G>C	p.Val16Leu	missense	Exon 1 of 31	ENSP00000555000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398138 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689588

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.0000280 AC: 1 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078862

Other (OTH) AF: 0.00 AC: 0 AN: 57986

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Benign	0.95
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.3
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.017
Sift	Benign	0.14	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.29		Gain of catalytic residue at M15 (P = 0.0502)
MVP		0.43
MPC		0.35
ClinPred		0.25	T
GERP RS		3.2
PromoterAI		0.0024	Neutral
gMVP		0.46
Mutation Taster		=93/7	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr13-113623739;