dbSNP rs762492880: MORF4L2:p.Pro10Arg (chrX-103676999-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_012286.3(MORF4L2):c.29C>G(p.Pro10Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,196,768 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000092 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.000023 ( 0 hom. 9 hem. )

Consequence

MORF4L2
NM_012286.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

Publications

0 publications found

Variant links:

Genes affected

MORF4L2 (HGNC:16849): (mortality factor 4 like 2) Predicted to be involved in heterochromatin assembly and histone modification. Predicted to act upstream of or within positive regulation of striated muscle cell differentiation and positive regulation of transcription by RNA polymerase II. Located in nucleolus; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MORF4L2 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=0.12814376).

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012286.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MORF4L2	NM_012286.3	MANE Select	c.29C>G	p.Pro10Arg	missense	Exon 4 of 4	NP_036418.1	Q15014
MORF4L2	NM_001142418.2		c.29C>G	p.Pro10Arg	missense	Exon 5 of 5	NP_001135890.1	Q15014
MORF4L2	NM_001142419.2		c.29C>G	p.Pro10Arg	missense	Exon 4 of 4	NP_001135891.1	Q15014

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MORF4L2	ENST00000441076.7	TSL:1 MANE Select	c.29C>G	p.Pro10Arg	missense	Exon 4 of 4	ENSP00000391969.2	Q15014
MORF4L2	ENST00000467755.5	TSL:1	n.350C>G		non_coding_transcript_exon	Exon 4 of 4
MORF4L2	ENST00000360458.5	TSL:2	c.29C>G	p.Pro10Arg	missense	Exon 4 of 4	ENSP00000353643.1	Q15014

Frequencies

GnomAD3 genomes

AF:

0.00000921

AC:

AN:

108621

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000177

AC:

AN:

169301

AF XY:

0.0000175

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000396

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000230

AC:

AN:

1088147

Hom.:

Cov.:

AF XY:

0.0000253

AC XY:

AN XY:

355895

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25616

American (AMR)

AF:

0.00

AC:

AN:

33142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18891

East Asian (EAS)

AF:

0.00

AC:

AN:

29985

South Asian (SAS)

AF:

0.00

AC:

AN:

51862

European-Finnish (FIN)

AF:

0.0000248

AC:

AN:

40276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3897

European-Non Finnish (NFE)

AF:

0.0000250

AC:

AN:

838860

Other (OTH)

AF:

0.0000658

AC:

AN:

45618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00000921

AC:

AN:

108621

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30959

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29727

American (AMR)

AF:

0.00

AC:

AN:

9999

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2606

East Asian (EAS)

AF:

0.00

AC:

AN:

3437

South Asian (SAS)

AF:

0.00

AC:

AN:

2487

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

52512

Other (OTH)

AF:

0.00

AC:

AN:

1460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000162

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.19

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.080

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.64

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

4.5

PrimateAI

Benign

0.42

PROVEAN

Benign

0.62

REVEL

Benign

0.046

Sift

Benign

0.12

Sift4G

Benign

0.45

Polyphen

0.032

Vest4

0.14

MutPred

0.26

Gain of MoRF binding (P = 0.0093)

MVP

0.60

ClinPred

0.064

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.44

Mutation Taster

=100/0

polymorphism

(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