dbSNP rs77416189: MEIOC:p.Tyr634Cys (chr17-44667812-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001145080.3(MEIOC):c.1901A>G(p.Tyr634Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0132 in 1,613,878 control chromosomes in the GnomAD database, including 355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 61 hom., cov: 32)

Exomes 𝑓: 0.013 ( 294 hom. )

Consequence

MEIOC
NM_001145080.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.51

Publications

5 publications found

Variant links:

Genes affected

MEIOC (HGNC:26670): (meiosis specific with coiled-coil domain) Predicted to be involved in several processes, including gamete generation; germline cell cycle switching, mitotic to meiotic cell cycle; and mRNA stabilization. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MEIOC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048514307).

BP6

Variant 17-44667812-A-G is Benign according to our data. Variant chr17-44667812-A-G is described in ClinVar as Benign. ClinVar VariationId is 3387873.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 61 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145080.3. 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
	MEIOC	NM_001145080.3	MANE Select	c.1901A>G	p.Tyr634Cys	missense	Exon 5 of 8	NP_001138552.2	A2RUB1-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEIOC	ENST00000409122.7	TSL:5 MANE Select	c.1901A>G	p.Tyr634Cys	missense	Exon 5 of 8	ENSP00000386452.1	A2RUB1-4
MEIOC	ENST00000856682.1		c.1796A>G	p.Tyr599Cys	missense	Exon 4 of 7	ENSP00000526741.1
MEIOC	ENST00000409464.1	TSL:2	c.1403A>G	p.Tyr468Cys	missense	Exon 2 of 3	ENSP00000386586.1	A2RUB1-1

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2112

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.00890

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0789

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0149

Gnomad OTH

AF:

0.00861

GnomAD2 exomes

AF:

0.0151

AC:

3788

AN:

250700

AF XY:

0.0150

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00388

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0768

Gnomad NFE exome

AF:

0.0157

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0132

AC:

19261

AN:

1461524

Hom.:

294

Cov.:

AF XY:

0.0128

AC XY:

9315

AN XY:

727026

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

33480

American (AMR)

AF:

0.00360

AC:

161

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00188

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00304

AC:

262

AN:

86224

European-Finnish (FIN)

AF:

0.0772

AC:

4118

AN:

53376

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0125

AC:

13867

AN:

1111780

Other (OTH)

AF:

0.0124

AC:

747

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1090

2180

3269

4359

5449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

462

924

1386

1848

2310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0139

AC:

2113

AN:

152354

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1227

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41586

American (AMR)

AF:

0.00889

AC:

136

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00269

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0789

AC:

837

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0149

AC:

1011

AN:

68038

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

105

209

314

418

523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.00747

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.0122

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0129

AC:

111

ExAC

AF:

0.0153

AC:

1859

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00981

EpiControl

AF:

0.0113

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.90

PhyloP100

6.5

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.26

Sift

Uncertain

0.0030

Sift4G

Benign

0.099

Polyphen

1.0

Vest4

0.63

MPC

0.35

ClinPred

0.025

GERP RS

5.7

Varity_R

0.17

gMVP

0.42

Mutation Taster

=86/14

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over