chr4-89895527-C-T

Variant names:

• chr4-89895527-C-T
• rs1475130595
• NM_007351.3:c.556C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007351.3(MMRN1):​c.556C>T​(p.Arg186Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: MMRN1 NM_007351.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.817
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41105103).

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.556C>T	p.Arg186Trp	missense	Exon 1 of 8	NP_031377.2
	MMRN1	NM_001371403.1		c.556C>T	p.Arg186Trp	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.556C>T	p.Arg186Trp	missense	Exon 1 of 8	ENSP00000264790.2	Q13201-1
	MMRN1	ENST00000394980.5	TSL:5	c.556C>T	p.Arg186Trp	missense	Exon 2 of 9	ENSP00000378431.1	Q13201-1
	MMRN1	ENST00000955234.1		c.556C>T	p.Arg186Trp	missense	Exon 1 of 8	ENSP00000625293.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250594 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461528 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 727072

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000758 AC: 3 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.15
BayesDel_addAF	Benign	-0.0084	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.036
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.82
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.46		Loss of sheet (P = 0.0084)
MVP		0.62
MPC		0.084
ClinPred		0.72	D
GERP RS		2.1
Varity_R		0.087
gMVP		0.29
Mutation Taster		=89/11	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: rs1475130595; hg19: chr4-90816678;