NM_024756.3:c.2017C>T

Variant names:

• chr10-86942767-G-A
• rs1171422014
• NM_024756.3:c.2017C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024756.3(MMRN2):​c.2017C>T​(p.Arg673Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000655 in 1,373,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: MMRN2 NM_024756.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.225
• Publications: 0 publications found

Genes affected

MMRN2 (HGNC:19888): (multimerin 2) This gene encodes a protein belonging to the member of elastin microfibril interface-located (EMILIN) protein family. This family member is an extracellular matrix glycoprotein that can interfere with tumor angiogenesis and growth. It serves as a transforming growth factor beta antagonist and can interfere with the VEGF-A/VEGFR2 pathway. A related pseudogene has been identified on chromosome 6. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08414039).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024756.3. 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
	MMRN2	NM_024756.3	MANE Select	c.2017C>T	p.Arg673Trp	missense	Exon 6 of 7	NP_079032.2	Q9H8L6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMRN2	ENST00000372027.10	TSL:1 MANE Select	c.2017C>T	p.Arg673Trp	missense	Exon 6 of 7	ENSP00000361097.4	Q9H8L6
	MMRN2	ENST00000896191.1		c.2047C>T	p.Arg683Trp	missense	Exon 6 of 7	ENSP00000566250.1
	MMRN2	ENST00000896187.1		c.2017C>T	p.Arg673Trp	missense	Exon 7 of 8	ENSP00000566246.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151908 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 19182 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000655 AC: 8 AN: 1221232 Hom.: 0 Cov.: 33 AF XY: 0.00000844 AC XY: 5 AN XY: 592542

African (AFR) AF: 0.00 AC: 0 AN: 23788

American (AMR) AF: 0.00 AC: 0 AN: 12308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16914

East Asian (EAS) AF: 0.00 AC: 0 AN: 27260

South Asian (SAS) AF: 0.00 AC: 0 AN: 54990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4082

European-Non Finnish (NFE) AF: 0.00000599 AC: 6 AN: 1002028

Other (OTH) AF: 0.0000400 AC: 2 AN: 49986

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151908 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74204

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67948

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000151

Asia WGS AF: 0.000588 AC: 2 AN: 3418

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	0.098
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.23
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.024
Sift	Uncertain	0.016	D
Sift4G	Benign	0.11	T
Polyphen		0.096	B
Vest4		0.18
MutPred		0.22		Gain of catalytic residue at R673 (P = 0.0222)
MVP		0.22
MPC		1.7
ClinPred		0.12	T
GERP RS		-4.6
Varity_R		0.042
gMVP		0.24
Mutation Taster		=99/1	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: rs1171422014; hg19: chr10-88702524;