rs7639705

Positions:

• chr3-183309754-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015078.4(MCF2L2):​c.1075A>C​(p.Ile359Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,322 control chromosomes in the GnomAD database, including 43,514 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.27 (6290 hom., cov: 30)
  • Exomes 𝑓: 0.22 (37224 hom.)
• Consequence: MCF2L2 NM_015078.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006294757).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCF2L2	NM_015078.4	c.1075A>C	p.Ile359Leu	missense_variant	10/30	ENST00000328913.8	NP_055893.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCF2L2	ENST00000328913.8	c.1075A>C	p.Ile359Leu	missense_variant	10/30	5	NM_015078.4	ENSP00000328118	A2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41315 AN: 151452 Hom.: 6273 Cov.: 30

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.236

GnomAD3 exomes AF: 0.257 AC: 64609 AN: 251424 Hom.: 9018 AF XY: 0.253 AC XY: 34403 AN XY: 135882

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.371

Gnomad SAS exome AF: 0.325

Gnomad FIN exome AF: 0.254

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.237

GnomAD4 exome AF: 0.218 AC: 318965 AN: 1461752 Hom.: 37224 Cov.: 33 AF XY: 0.220 AC XY: 159661 AN XY: 727192

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.365

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.273 AC: 41382 AN: 151570 Hom.: 6290 Cov.: 30 AF XY: 0.276 AC XY: 20444 AN XY: 74022

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.239

Alfa AF: 0.211 Hom.: 9014

Bravo AF: 0.280

TwinsUK AF: 0.195 AC: 723

ALSPAC AF: 0.183 AC: 706

ESP6500AA AF: 0.400 AC: 1762

ESP6500EA AF: 0.196 AC: 1689

ExAC AF: 0.256 AC: 31121

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.26
DEOGEN2	Benign	0.0019	T;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.039	T;T;T;T
MetaRNN	Benign	0.0063	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.7	N;N;N;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.77	N;N;N;N
REVEL	Benign	0.099
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;.;B;.
Vest4		0.091
MPC		0.18
ClinPred		0.0025	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.068
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs7639705; hg19: chr3-183027542; COSMIC: COSV61049340; COSMIC: COSV61049340;