10-14966512-A-G

Position:

• chr10-14966512-A-G

Variant summary

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

The NM_001080836.3(MEIG1):​c.44A>G​(p.Lys15Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,472 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MEIG1 NM_001080836.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

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 (HGNC:):

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	Protein	UniProt
MEIG1	NM_001080836.3	c.44A>G	p.Lys15Arg	missense_variant	2/3	ENST00000407572.6	NP_001074305.1
MEIG1	XM_024448136.1	c.137A>G	p.Lys46Arg	missense_variant	2/3		XP_024303904.1
MEIG1	XM_047425662.1	c.44A>G	p.Lys15Arg	missense_variant	2/3		XP_047281618.1
MEIG1	NR_147060.2	n.170+6955A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIG1	ENST00000407572.6	c.44A>G	p.Lys15Arg	missense_variant	2/3	2	NM_001080836.3	ENSP00000384334.1
MEIG1	ENST00000378240.1	c.44A>G	p.Lys15Arg	missense_variant	1/2	2		ENSP00000367486.1
MEIG1	ENST00000477770.5	n.120-6001A>G		intron_variant		2
MEIG1	ENST00000496225.2	n.49-3736A>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460472 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726510

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

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

May 01, 2022

The c.44A>G (p.K15R) alteration is located in exon 2 (coding exon 1) of the MEIG1 gene. This alteration results from a A to G substitution at nucleotide position 44, causing the lysine (K) at amino acid position 15 to be replaced by an arginine (R). 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	0.078
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	T;.
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.33	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.15
Sift	Benign	0.045	D;D
Sift4G	Benign	0.099	T;T
Polyphen		1.0	D;D
Vest4		0.40
MutPred		0.19		Loss of ubiquitination at K15 (P = 0.0118);Loss of ubiquitination at K15 (P = 0.0118);
MVP		0.46
MPC		0.026
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.51
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-15008511;