15-56429208-C-T

Position:

• chr15-56429208-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018365.4(MNS1):​c.1396-15G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,538,092 control chromosomes in the GnomAD database, including 767,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (75512 hom., cov: 31)
  • Exomes 𝑓: 1.0 (692185 hom.)
• Consequence: MNS1 NM_018365.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0980

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 15-56429208-C-T is Benign according to our data. Variant chr15-56429208-C-T is described in ClinVar as [Benign]. Clinvar id is 1235571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX9	NM_001395496.1	c.*764C>T		3_prime_UTR_variant	12/12	ENST00000696102.1	NP_001382425.1
MNS1	NM_018365.4	c.1396-15G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000260453.4	NP_060835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX9	ENST00000696102.1	c.*764C>T		3_prime_UTR_variant	12/12		NM_001395496.1	ENSP00000512397	P1
MNS1	ENST00000260453.4	c.1396-15G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018365.4	ENSP00000260453	P1

Frequencies

GnomAD3 genomes AF: 0.996 AC: 151499 AN: 152090 Hom.: 75455 Cov.: 31

Gnomad AFR AF: 0.987

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.996

GnomAD3 exomes AF: 0.999 AC: 219154 AN: 219408 Hom.: 109453 AF XY: 0.999 AC XY: 119286 AN XY: 119396

Gnomad AFR exome AF: 0.988

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 0.997

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome AF: 0.999 AC: 1385127 AN: 1385884 Hom.: 692185 Cov.: 23 AF XY: 0.999 AC XY: 691424 AN XY: 691802

Gnomad4 AFR exome AF: 0.988

Gnomad4 AMR exome AF: 0.999

Gnomad4 ASJ exome AF: 0.998

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.999

GnomAD4 genome AF: 0.996 AC: 151615 AN: 152208 Hom.: 75512 Cov.: 31 AF XY: 0.996 AC XY: 74133 AN XY: 74416

Gnomad4 AFR AF: 0.987

Gnomad4 AMR AF: 0.998

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.996

Alfa AF: 1.00 Hom.: 62234

Bravo AF: 0.996

Asia WGS AF: 1.00 AC: 3461 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 30, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.56

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: rs808730; hg19: chr15-56721406;