rs6493858

Positions:

• chr15-56444280-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNS1	NM_018365.4	c.686+164C>T		intron_variant		ENST00000260453.4	NP_060835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNS1	ENST00000260453.4	c.686+164C>T		intron_variant		1	NM_018365.4	ENSP00000260453.3
TEX9	ENST00000352903.6	c.*30-1391G>A		intron_variant		1		ENSP00000342169.2
TEX9	ENST00000537232.5	n.*1306-1391G>A		intron_variant		2		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

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.403

Alfa AF: 0.437 Hom.: 24761

Bravo AF: 0.448

Asia WGS AF: 0.357 AC: 1240 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.24
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs6493858; hg19: chr15-56736478;