Genetic Variant NM_001037225.3:c.154G>A (chr11-64950424-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001037225.3(MAJIN):c.154G>A(p.Val52Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MAJIN
NM_001037225.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.981

Publications

0 publications found

Variant links:

Genes affected

MAJIN (HGNC:27441): (membrane anchored junction protein) Predicted to enable DNA binding activity. Predicted to be involved in homologous chromosome pairing at meiosis and meiotic attachment of telomere to nuclear envelope. Predicted to be located in chromosome, telomeric region. Predicted to be integral component of nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

MAJIN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026290476).

BP6

Variant 11-64950424-C-T is Benign according to our data. Variant chr11-64950424-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3122301.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037225.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAJIN	NM_001037225.3	MANE Select	c.154G>A	p.Val52Ile	missense	Exon 5 of 11	NP_001032302.1	Q3KP22-3
MAJIN	NM_001318808.2		c.-165G>A		5_prime_UTR	Exon 5 of 12	NP_001305737.1	Q3KP22-4
MAJIN	NM_001300803.2		c.148-2959G>A		intron	N/A	NP_001287732.1	Q3KP22-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAJIN	ENST00000301896.6	TSL:5 MANE Select	c.154G>A	p.Val52Ile	missense	Exon 5 of 11	ENSP00000301896.5	Q3KP22-3
MAJIN	ENST00000432175.5	TSL:1	c.154G>A	p.Val52Ile	missense	Exon 4 of 10	ENSP00000395273.1	Q3KP22-3
MAJIN	ENST00000530444.5	TSL:1	c.148-2959G>A		intron	N/A	ENSP00000434568.1	Q3KP22-1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000438

AC:

AN:

251282

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1460974

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726832

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.000291

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111308

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000264

AC:

AN:

151624

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74020

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41380

American (AMR)

AF:

0.000263

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67960

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.1

(source)

DANN

Benign

0.27

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.50

M_CAP

Benign

0.0025

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.98

PhyloP100

0.98

PROVEAN

Benign

0.45

REVEL

Benign

0.081

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.25

MVP

0.20

MPC

0.047

ClinPred

0.024

GERP RS

4.0

gMVP

0.12

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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