15-56444280-G-A

Variant names:

• chr15-56444280-G-A
• rs6493858
• NM_018365.4:c.686+164C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018365.4(MNS1):​c.686+164C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,726 control chromosomes in the GnomAD database, including 15,400 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15400 hom., cov: 32)
• Consequence: MNS1 NM_018365.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 8 publications found

Genes affected

MNS1 (HGNC:29636): (meiosis specific nuclear structural 1) This gene encodes a protein highly similar to the mouse meiosis-specific nuclear structural 1 protein. The mouse protein was shown to be expressed at the pachytene stage during spermatogenesis and may function as a nuclear skeletal protein to regulate nuclear morphology during meiosis. [provided by RefSeq, Oct 2008]

TEX9 (HGNC:29585): (testis expressed 9)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018365.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNS1	NM_018365.4	MANE Select	c.686+164C>T		intron	N/A	NP_060835.1
	TEX9	NM_198524.3		c.*30-1391G>A		intron	N/A	NP_940926.1
	TEX9	NM_001286449.2		c.*30-1391G>A		intron	N/A	NP_001273378.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNS1	ENST00000260453.4	TSL:1 MANE Select	c.686+164C>T		intron	N/A	ENSP00000260453.3
	TEX9	ENST00000352903.6	TSL:1	c.*30-1391G>A		intron	N/A	ENSP00000342169.2
	TEX9	ENST00000537232.5	TSL:2	n.*1306-1391G>A		intron	N/A	ENSP00000438745.2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67838 AN: 151610 Hom.: 15387 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.447 AC: 67890 AN: 151726 Hom.: 15400 Cov.: 32 AF XY: 0.443 AC XY: 32885 AN XY: 74166

African (AFR) AF: 0.498 AC: 20645 AN: 41428

American (AMR) AF: 0.407 AC: 6201 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1344 AN: 3462

East Asian (EAS) AF: 0.347 AC: 1796 AN: 5176

South Asian (SAS) AF: 0.315 AC: 1517 AN: 4810

European-Finnish (FIN) AF: 0.445 AC: 4692 AN: 10546

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.447 AC: 30266 AN: 67746

Other (OTH) AF: 0.403 AC: 850 AN: 2110

Alfa AF: 0.441 Hom.: 41899

Bravo AF: 0.448

Asia WGS AF: 0.357 AC: 1240 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.24
DANN	Benign	0.55
PhyloP100		-0.16
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: rs6493858; hg19: chr15-56736478;