Variant 10-14966577-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001080836.3(MEIG1):c.109G>A(p.Glu37Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,610,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

MEIG1
NM_001080836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.15

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIG1	NM_001080836.3 linkuse as main transcript	c.109G>A	p.Glu37Lys	missense_variant	2/3	ENST00000407572.6	NP_001074305.1	Q5JSS6
MEIG1	XM_024448136.1 linkuse as main transcript	c.202G>A	p.Glu68Lys	missense_variant	2/3		XP_024303904.1
MEIG1	XM_047425662.1 linkuse as main transcript	c.109G>A	p.Glu37Lys	missense_variant	2/3		XP_047281618.1
MEIG1	NR_147060.2 linkuse as main transcript	n.170+7020G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MEIG1	ENST00000407572.6 linkuse as main transcript	c.109G>A	p.Glu37Lys	missense_variant	2/3	2	NM_001080836.3	ENSP00000384334.1	Q5JSS6
MEIG1	ENST00000378240.1 linkuse as main transcript	c.109G>A	p.Glu37Lys	missense_variant	1/2	2		ENSP00000367486.1	Q5JSS6
MEIG1	ENST00000477770.5 linkuse as main transcript	n.120-5936G>A		intron_variant		2
MEIG1	ENST00000496225.2 linkuse as main transcript	n.49-3671G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000483

AC:

AN:

248418

Hom.:

AF XY:

0.0000820

AC XY:

AN XY:

134182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000697

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1458748

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

725502

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000652

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000586

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000577

AC:

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

Sep 14, 2021

The c.109G>A (p.E37K) alteration is located in exon 2 (coding exon 1) of the MEIG1 gene. This alteration results from a G to A substitution at nucleotide position 109, causing the glutamic acid (E) at amino acid position 37 to be replaced by a lysine (K). 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

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.65

D;D

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;.

M_CAP

Uncertain

0.099

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Uncertain

-0.23

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.94

MVP

0.49

MPC

0.23

ClinPred

0.91

GERP RS

5.7

Varity_R

0.92

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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