Variant 10-14966513-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001080836.3(MEIG1):c.45A>C(p.Lys15Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

MEIG1
NM_001080836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

MEIG1 (HGNC:23429): (meiosis/spermiogenesis associated 1) Predicted to act upstream of or within cellular protein localization; manchette assembly; and sperm axoneme assembly. Predicted to be located in cytosol and manchette. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MEIG1 links:

MEIG1 (HGNC:):

MEIG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
MEIG1	NM_001080836.3 linkuse as main transcript	c.45A>C	p.Lys15Asn	missense_variant	2/3	ENST00000407572.6	NP_001074305.1	Q5JSS6
MEIG1	XM_024448136.1 linkuse as main transcript	c.138A>C	p.Lys46Asn	missense_variant	2/3		XP_024303904.1
MEIG1	XM_047425662.1 linkuse as main transcript	c.45A>C	p.Lys15Asn	missense_variant	2/3		XP_047281618.1
MEIG1	NR_147060.2 linkuse as main transcript	n.170+6956A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MEIG1	ENST00000407572.6 linkuse as main transcript	c.45A>C	p.Lys15Asn	missense_variant	2/3	2	NM_001080836.3	ENSP00000384334.1	Q5JSS6
MEIG1	ENST00000378240.1 linkuse as main transcript	c.45A>C	p.Lys15Asn	missense_variant	1/2	2		ENSP00000367486.1	Q5JSS6
MEIG1	ENST00000477770.5 linkuse as main transcript	n.120-6000A>C		intron_variant		2
MEIG1	ENST00000496225.2 linkuse as main transcript	n.49-3735A>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.45A>C (p.K15N) alteration is located in exon 2 (coding exon 1) of the MEIG1 gene. This alteration results from a A to C substitution at nucleotide position 45, causing the lysine (K) at amino acid position 15 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

Benign

0.33

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.75

T;.

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.48

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.1

D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

1.0

D;D

Vest4

0.50

MutPred

0.20

Loss of methylation at K15 (P = 0.0114);Loss of methylation at K15 (P = 0.0114);

MVP

0.43

MPC

0.10

ClinPred

0.98

GERP RS

3.4

Varity_R

0.87

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over