13-112969383-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_001112732.3(MCF2L):c.4A>C(p.Arg2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,549,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: MCF2L NM_001112732.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.45

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

Verdict is Benign. Variant got -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 13-112969383-A-C is Benign according to our data. Variant chr13-112969383-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 741303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.45 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2L	NM_001112732.3	c.4A>C	p.Arg2=	synonymous_variant	1/30	ENST00000535094.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2L	ENST00000535094.7	c.4A>C	p.Arg2=	synonymous_variant	1/30	2	NM_001112732.3	A1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000170 AC: 25 AN: 147048 Hom.: 0 AF XY: 0.000101 AC XY: 8 AN XY: 79278

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000326

Gnomad ASJ exome AF: 0.000358

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.000468

GnomAD4 exome AF: 0.000127 AC: 177 AN: 1397852 Hom.: 0 Cov.: 31 AF XY: 0.000103 AC XY: 71 AN XY: 689464

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000308

Gnomad4 ASJ exome AF: 0.000914

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000125

Gnomad4 OTH exome AF: 0.000104

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74304

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.000159

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	MCF2L: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jun 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	9.0
Dann	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs777895059; hg19: chr13-113623697;