chr13-113014845-C-T

Variant names:

• chr13-113014845-C-T
• rs149468042
• NM_001112732.3:c.162C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001112732.3(MCF2L):​c.162C>T​(p.Ser54Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00034 in 1,612,896 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (3 hom.)
• Consequence: MCF2L NM_001112732.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002874
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.174
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 13-113014845-C-T is Benign according to our data. Variant chr13-113014845-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 724768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.174 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.162C>T	p.Ser54Ser	splice_region synonymous	Exon 2 of 30	NP_001106203.2	O15068-9
	MCF2L	NM_001438390.1		c.261C>T	p.Ser87Ser	splice_region synonymous	Exon 2 of 32	NP_001425319.1
	MCF2L	NM_001438391.1		c.252C>T	p.Ser84Ser	splice_region synonymous	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.162C>T	p.Ser54Ser	splice_region synonymous	Exon 2 of 30	ENSP00000440374.2	O15068-9
	MCF2L	ENST00000421756.5	TSL:1	c.174C>T	p.Ser58Ser	splice_region synonymous	Exon 2 of 28	ENSP00000397285.1	O15068-3
	MCF2L	ENST00000375597.8	TSL:1	c.156C>T	p.Ser52Ser	splice_region synonymous	Exon 2 of 27	ENSP00000364747.4	O15068-4

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 152172 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000422 AC: 106 AN: 250996 AF XY: 0.000317

Gnomad AFR exome AF: 0.00505

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000224 AC: 327 AN: 1460606 Hom.: 3 Cov.: 31 AF XY: 0.000208 AC XY: 151 AN XY: 726506

African (AFR) AF: 0.00535 AC: 179 AN: 33470

American (AMR) AF: 0.000537 AC: 24 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39686

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53028

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5766

European-Non Finnish (NFE) AF: 0.0000693 AC: 77 AN: 1111252

Other (OTH) AF: 0.000530 AC: 32 AN: 60354

GnomAD4 genome AF: 0.00145 AC: 221 AN: 152290 Hom.: 2 Cov.: 33 AF XY: 0.00153 AC XY: 114 AN XY: 74458

African (AFR) AF: 0.00472 AC: 196 AN: 41566

American (AMR) AF: 0.00124 AC: 19 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000304 Hom.: 0

Bravo AF: 0.00173

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.23
DANN	Benign	0.85
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.048
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: rs149468042; hg19: chr13-113669159; COSMIC: COSV65053343; COSMIC: COSV65053343;