chr15-56429175-C-T

Variant names:

• chr15-56429175-C-T
• rs564126888
• NM_018365.4:c.1414G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018365.4(MNS1):​c.1414G>A​(p.Asp472Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000941 in 1,594,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: MNS1 NM_018365.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042129576).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNS1	NM_018365.4	MANE Select	c.1414G>A	p.Asp472Asn	missense	Exon 10 of 10	NP_060835.1	Q8NEH6
	TEX9	NM_001395496.1	MANE Select	c.*731C>T		3_prime_UTR	Exon 12 of 12	NP_001382425.1	A0A0S2Z669
	TEX9	NM_001385046.1		c.*731C>T		3_prime_UTR	Exon 10 of 10	NP_001371975.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNS1	ENST00000260453.4	TSL:1 MANE Select	c.1414G>A	p.Asp472Asn	missense	Exon 10 of 10	ENSP00000260453.3	Q8NEH6
	TEX9	ENST00000696102.1	MANE Select	c.*731C>T		3_prime_UTR	Exon 12 of 12	ENSP00000512397.1	Q8N6V9-1
	TEX9	ENST00000352903.6	TSL:1	c.*29+702C>T		intron	N/A	ENSP00000342169.2	Q8N6V9-1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151996 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000129 AC: 3 AN: 232106 AF XY: 0.0000239

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000277

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000901 AC: 13 AN: 1442552 Hom.: 0 Cov.: 30 AF XY: 0.0000139 AC XY: 10 AN XY: 717310

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000310 AC: 1 AN: 32272

American (AMR) AF: 0.00 AC: 0 AN: 40894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25750

East Asian (EAS) AF: 0.00 AC: 0 AN: 38906

South Asian (SAS) AF: 0.00 AC: 0 AN: 82368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000996 AC: 11 AN: 1104312

Other (OTH) AF: 0.0000167 AC: 1 AN: 59782

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000183758), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41540

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000283 Hom.: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.1
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.076
Sift	Benign	0.20	T
Sift4G	Benign	0.39	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.33		Gain of methylation at K470 (P = 0.0832)
MVP		0.13
MPC		0.028
ClinPred		0.39	T
GERP RS		4.0
Varity_R		0.041
gMVP		0.40
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs564126888; hg19: chr15-56721373;