4-89895490-C-T

Variant names:

• chr4-89895490-C-T
• rs61741915
• NM_007351.3:c.519C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_007351.3(MMRN1):​c.519C>T​(p.Gly173Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,613,716 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (56 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (60 hom.)
• Consequence: MMRN1 NM_007351.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.20
• Publications: 2 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 4-89895490-C-T is Benign according to our data. Variant chr4-89895490-C-T is described in ClinVar as Benign. ClinVar VariationId is 789579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.2 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

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.519C>T	p.Gly173Gly	synonymous	Exon 1 of 8	NP_031377.2
	MMRN1	NM_001371403.1		c.519C>T	p.Gly173Gly	synonymous	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.519C>T	p.Gly173Gly	synonymous	Exon 1 of 8	ENSP00000264790.2	Q13201-1
	MMRN1	ENST00000394980.5	TSL:5	c.519C>T	p.Gly173Gly	synonymous	Exon 2 of 9	ENSP00000378431.1	Q13201-1
	MMRN1	ENST00000955234.1		c.519C>T	p.Gly173Gly	synonymous	Exon 1 of 8	ENSP00000625293.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2192 AN: 152042 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00531

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00410 AC: 1028 AN: 250518 AF XY: 0.00312

Gnomad AFR exome AF: 0.0520

Gnomad AMR exome AF: 0.00258

Gnomad ASJ exome AF: 0.00289

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000371

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00195 AC: 2847 AN: 1461556 Hom.: 60 Cov.: 34 AF XY: 0.00173 AC XY: 1261 AN XY: 727072

African (AFR) AF: 0.0578 AC: 1933 AN: 33466

American (AMR) AF: 0.00293 AC: 131 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00298 AC: 78 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86252

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53408

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5766

European-Non Finnish (NFE) AF: 0.000362 AC: 402 AN: 1111882

Other (OTH) AF: 0.00421 AC: 254 AN: 60386

GnomAD4 genome AF: 0.0145 AC: 2204 AN: 152160 Hom.: 56 Cov.: 32 AF XY: 0.0145 AC XY: 1076 AN XY: 74380

African (AFR) AF: 0.0495 AC: 2055 AN: 41500

American (AMR) AF: 0.00530 AC: 81 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68000

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.00662 Hom.: 14

Bravo AF: 0.0174

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: 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	-0.64
CADD	Benign	2.4
DANN	Benign	0.64
PhyloP100		-2.2
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: rs61741915; hg19: chr4-90816641;