NM_015078.4:c.1075A>C

Variant names:

• chr3-183309754-T-G
• rs7639705
• NM_015078.4:c.1075A>C

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015078.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2L2	NM_015078.4	MANE Select	c.1075A>C	p.Ile359Leu	missense	Exon 10 of 30	NP_055893.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2L2	ENST00000328913.8	TSL:5 MANE Select	c.1075A>C	p.Ile359Leu	missense	Exon 10 of 30	ENSP00000328118.3
	MCF2L2	ENST00000447025.6	TSL:1	c.1075A>C	p.Ile359Leu	missense	Exon 10 of 18	ENSP00000388190.2
	MCF2L2	ENST00000459750.5	TSL:1	n.1282A>C		non_coding_transcript_exon	Exon 11 of 12

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

GnomAD2 exomes AF: 0.257 AC: 64609 AN: 251424 AF XY: 0.253

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 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

African (AFR) AF: 0.407 AC: 13608 AN: 33474

American (AMR) AF: 0.282 AC: 12621 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6049 AN: 26136

East Asian (EAS) AF: 0.365 AC: 14485 AN: 39700

South Asian (SAS) AF: 0.316 AC: 27278 AN: 86254

European-Finnish (FIN) AF: 0.248 AC: 13255 AN: 53414

Middle Eastern (MID) AF: 0.212 AC: 1221 AN: 5768

European-Non Finnish (NFE) AF: 0.195 AC: 216381 AN: 1111906

Other (OTH) AF: 0.233 AC: 14067 AN: 60386

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

African (AFR) AF: 0.396 AC: 16351 AN: 41262

American (AMR) AF: 0.272 AC: 4139 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 796 AN: 3466

East Asian (EAS) AF: 0.364 AC: 1850 AN: 5088

South Asian (SAS) AF: 0.325 AC: 1561 AN: 4800

European-Finnish (FIN) AF: 0.255 AC: 2675 AN: 10482

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13163 AN: 67952

Other (OTH) AF: 0.239 AC: 501 AN: 2098

Alfa AF: 0.220 Hom.: 14528

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 v4.9

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
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.7	N
PhyloP100		2.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.77	N
REVEL	Benign	0.099
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	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
Mutation Taster		=100/0	polymorphism (auto)

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