chr15-56429168-A-T

Position:

• chr15-56429168-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018365.4(MNS1):​c.1421T>A​(p.Ile474Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MNS1 NM_018365.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.50

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNS1	NM_018365.4	c.1421T>A	p.Ile474Asn	missense_variant	10/10	ENST00000260453.4
TEX9	NM_001395496.1	c.*724A>T		3_prime_UTR_variant	12/12	ENST00000696102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNS1	ENST00000260453.4	c.1421T>A	p.Ile474Asn	missense_variant	10/10	1	NM_018365.4	P1
TEX9	ENST00000696102.1	c.*724A>T		3_prime_UTR_variant	12/12		NM_001395496.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.1421T>A (p.I474N) alteration is located in exon 10 (coding exon 10) of the MNS1 gene. This alteration results from a T to A substitution at nucleotide position 1421, causing the isoleucine (I) at amino acid position 474 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.76	D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.24
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.92	P
Vest4		0.53
MutPred		0.57		Gain of disorder (P = 0.013);
MVP		0.50
MPC		0.18
ClinPred		0.94	D
GERP RS		6.1
Varity_R		0.55
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-56721366;