Genetic Variant MORF4L2:p.Val109Ile (chrX-103676703-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012286.3(MORF4L2):c.325G>A(p.Val109Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,097,255 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.0000046 ( 0 hom. 0 hem. )

Consequence

MORF4L2
NM_012286.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25272137).

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.325G>A	p.Val109Ile	missense	Exon 4 of 4	NP_036418.1	Q15014
MORF4L2	NM_001142418.2		c.325G>A	p.Val109Ile	missense	Exon 5 of 5	NP_001135890.1	Q15014
MORF4L2	NM_001142419.2		c.325G>A	p.Val109Ile	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.325G>A	p.Val109Ile	missense	Exon 4 of 4	ENSP00000391969.2	Q15014
MORF4L2	ENST00000360458.5	TSL:2	c.325G>A	p.Val109Ile	missense	Exon 4 of 4	ENSP00000353643.1	Q15014
MORF4L2	ENST00000433176.6	TSL:2	c.325G>A	p.Val109Ile	missense	Exon 4 of 4	ENSP00000415476.2	Q15014

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000552

AC:

AN:

181310

AF XY:

0.00

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:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1097255

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362643

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26359

American (AMR)

AF:

0.00

AC:

AN:

35117

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19315

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.00

AC:

AN:

53934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4115

European-Non Finnish (NFE)

AF:

0.00000594

AC:

AN:

841670

Other (OTH)

AF:

0.00

AC:

AN:

46045

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

0.27

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

3.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.81

REVEL

Benign

0.10

Sift

Benign

0.16

Sift4G

Benign

0.15

Polyphen

0.18

Vest4

0.39

MutPred

0.52

Gain of helix (P = 0.132)

MVP

0.52

MPC

0.83

ClinPred

0.41

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.39

Mutation Taster

=82/18

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over