rs181380349

Variant names:

• chr13-113014783-A-T
• rs181380349
• NM_001112732.3:c.100A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-113014783-A-T
• chr13-113014783-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001112732.3(MCF2L):​c.100A>T​(p.Ile34Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: MCF2L NM_001112732.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034085393).

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.100A>T	p.Ile34Phe	missense	Exon 2 of 30	NP_001106203.2	O15068-9
	MCF2L	NM_001438390.1		c.199A>T	p.Ile67Phe	missense	Exon 2 of 32	NP_001425319.1
	MCF2L	NM_001438391.1		c.190A>T	p.Ile64Phe	missense	Exon 3 of 33	NP_001425320.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2L	ENST00000535094.7	TSL:2 MANE Select	c.100A>T	p.Ile34Phe	missense	Exon 2 of 30	ENSP00000440374.2	O15068-9
	MCF2L	ENST00000421756.5	TSL:1	c.112A>T	p.Ile38Phe	missense	Exon 2 of 28	ENSP00000397285.1	O15068-3
	MCF2L	ENST00000375597.8	TSL:1	c.94A>T	p.Ile32Phe	missense	Exon 2 of 27	ENSP00000364747.4	O15068-4

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000876 AC: 22 AN: 251160 AF XY: 0.0000884

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00114

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000239 AC: 35 AN: 1461688 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 727122

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000731 AC: 29 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111944

Other (OTH) AF: 0.0000828 AC: 5 AN: 60396

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152294 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74474

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000110

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.17
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T
Eigen	Benign	0.087
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.2
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.047	D
Polyphen		0.60	P
Vest4		0.56
MVP		0.43
MPC		0.77
ClinPred		0.11	T
GERP RS		3.4
Varity_R		0.14
gMVP		0.46
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs181380349; hg19: chr13-113669097; COSMIC: COSV65050667; COSMIC: COSV65050667;