4-89895017-G-C

Variant names:

• chr4-89895017-G-C
• rs1721143598
• NM_007351.3:c.46G>C

Variant summary

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

The NM_007351.3(MMRN1):​c.46G>C​(p.Gly16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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 the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MMRN1 NM_007351.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 0 publications found

Genes affected

MMRN1 (HGNC:7178): (multimerin 1) Multimerin is a massive, soluble protein found in platelets and in the endothelium of blood vessels. It is comprised of subunits linked by interchain disulfide bonds to form large, variably sized homomultimers. Multimerin is a factor V/Va-binding protein and may function as a carrier protein for platelet factor V. It may also have functions as an extracellular matrix or adhesive protein. Recently, patients with an unusual autosomal-dominant bleeding disorder (factor V Quebec) were found to have a deficiency of platelet multimerin. [provided by RefSeq, Jul 2008]

MMRN1 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ENSG00000301182 (HGNC:58852):

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=0.09443605).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007351.3. 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
	MMRN1	NM_007351.3	MANE Select	c.46G>C	p.Gly16Arg	missense	Exon 1 of 8	NP_031377.2
	MMRN1	NM_001371403.1		c.46G>C	p.Gly16Arg	missense	Exon 2 of 9	NP_001358332.1	Q13201-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMRN1	ENST00000264790.7	TSL:1 MANE Select	c.46G>C	p.Gly16Arg	missense	Exon 1 of 8	ENSP00000264790.2	Q13201-1
	MMRN1	ENST00000394980.5	TSL:5	c.46G>C	p.Gly16Arg	missense	Exon 2 of 9	ENSP00000378431.1	Q13201-1
	MMRN1	ENST00000955234.1		c.46G>C	p.Gly16Arg	missense	Exon 1 of 8	ENSP00000625293.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.0
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.032
Sift	Benign	0.40	T
Sift4G	Benign	0.33	T
Polyphen		0.054	B
Vest4		0.23
MutPred		0.44		Gain of MoRF binding (P = 0.0081)
MVP		0.50
MPC		0.014
ClinPred		0.098	T
GERP RS		2.1
PromoterAI		0.0082	Neutral
Varity_R		0.019
gMVP		0.41
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1721143598; hg19: chr4-90816168;