rs4750568

Variant names:

• chr10-14966494-A-C
• rs4750568
• NM_001080836.3:c.26A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080836.3(MEIG1):​c.26A>C​(p.Lys9Thr) variant causes a missense change. The variant allele was found at a frequency of 0.669 in 1,607,570 control chromosomes in the GnomAD database, including 362,486 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (31583 hom., cov: 31)
  • Exomes 𝑓: 0.67 (330903 hom.)
• Consequence: MEIG1 NM_001080836.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87
• Publications: 28 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.392923E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIG1	NM_001080836.3	c.26A>C	p.Lys9Thr	missense_variant	Exon 2 of 3	ENST00000407572.6	NP_001074305.1
MEIG1	XM_024448136.1	c.119A>C	p.Lys40Thr	missense_variant	Exon 2 of 3		XP_024303904.1
MEIG1	XM_047425662.1	c.26A>C	p.Lys9Thr	missense_variant	Exon 2 of 3		XP_047281618.1
MEIG1	NR_147060.2	n.170+6937A>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIG1	ENST00000407572.6	c.26A>C	p.Lys9Thr	missense_variant	Exon 2 of 3	2	NM_001080836.3	ENSP00000384334.1
MEIG1	ENST00000378240.1	c.26A>C	p.Lys9Thr	missense_variant	Exon 1 of 2	2		ENSP00000367486.1
MEIG1	ENST00000477770.5	n.120-6019A>C		intron_variant	Intron 1 of 1	2
MEIG1	ENST00000496225.2	n.49-3754A>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97440 AN: 151854 Hom.: 31577 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.641

GnomAD2 exomes AF: 0.657 AC: 162190 AN: 247050 AF XY: 0.658

Gnomad AFR exome AF: 0.573

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.610

Gnomad EAS exome AF: 0.479

Gnomad FIN exome AF: 0.630

Gnomad NFE exome AF: 0.682

Gnomad OTH exome AF: 0.657

GnomAD4 exome AF: 0.672 AC: 978378 AN: 1455598 Hom.: 330903 Cov.: 35 AF XY: 0.672 AC XY: 486273 AN XY: 724044

African (AFR) AF: 0.573 AC: 19012 AN: 33198

American (AMR) AF: 0.718 AC: 31427 AN: 43800

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 15855 AN: 26062

East Asian (EAS) AF: 0.451 AC: 17804 AN: 39490

South Asian (SAS) AF: 0.669 AC: 56744 AN: 84830

European-Finnish (FIN) AF: 0.630 AC: 33631 AN: 53352

Middle Eastern (MID) AF: 0.691 AC: 3974 AN: 5750

European-Non Finnish (NFE) AF: 0.685 AC: 759829 AN: 1108898

Other (OTH) AF: 0.666 AC: 40102 AN: 60218

GnomAD4 genome AF: 0.642 AC: 97495 AN: 151972 Hom.: 31583 Cov.: 31 AF XY: 0.640 AC XY: 47546 AN XY: 74268

African (AFR) AF: 0.579 AC: 23965 AN: 41412

American (AMR) AF: 0.685 AC: 10455 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2089 AN: 3470

East Asian (EAS) AF: 0.471 AC: 2425 AN: 5154

South Asian (SAS) AF: 0.670 AC: 3228 AN: 4818

European-Finnish (FIN) AF: 0.627 AC: 6623 AN: 10558

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46544 AN: 67990

Other (OTH) AF: 0.643 AC: 1359 AN: 2114

Alfa AF: 0.665 Hom.: 117952

Bravo AF: 0.643

TwinsUK AF: 0.680 AC: 2520

ALSPAC AF: 0.685 AC: 2640

ESP6500AA AF: 0.585 AC: 2577

ESP6500EA AF: 0.688 AC: 5918

ExAC AF: 0.659 AC: 80011

Asia WGS AF: 0.615 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T;.
MetaRNN	Benign	0.0000084	T;T
MetaSVM	Benign	-0.97	T
PhyloP100		5.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.19
Sift	Benign	0.30	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.99	D;D
Vest4		0.21
MPC		0.054
ClinPred		0.038	T
GERP RS		5.7
PromoterAI		0.0068	Neutral
Varity_R		0.54
gMVP		0.52
Mutation Taster		=76/24	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4750568; hg19: chr10-15008493; COSMIC: COSV65542388;