Variant X-103676999-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 12/20 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

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12814376).

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORF4L2	NM_012286.3 linkuse as main transcript	c.29C>G	p.Pro10Arg	missense_variant	4/4	ENST00000441076.7	NP_036418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORF4L2	ENST00000441076.7 linkuse as main transcript	c.29C>G	p.Pro10Arg	missense_variant	4/4	1	NM_012286.3	ENSP00000391969	P1

Frequencies

GnomAD3 genomes

AF:

0.00000921

AC:

AN:

108621

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30959

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

GnomAD3 exomes

AF:

0.0000177

AC:

AN:

169301

Hom.:

AF XY:

0.0000175

AC XY:

AN XY:

57299

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000248

Gnomad4 NFE exome

AF:

0.0000250

Gnomad4 OTH exome

AF:

0.0000658

GnomAD4 genome

AF:

0.00000921

AC:

AN:

108621

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30959

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000190

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.29C>G (p.P10R) alteration is located in exon 5 (coding exon 1) of the MORF4L2 gene. This alteration results from a C to G substitution at nucleotide position 29, causing the proline (P) at amino acid position 10 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.25

DEOGEN2

Benign

0.080

T;T;T;T;T;.;.;.;.

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.64

.;.;T;.;.;.;T;T;T

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.13

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N;N;N;.;.;.;.

MutationTaster

Benign

1.0

D;N;N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.62

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.046

Sift

Benign

0.12

T;T;T;T;T;T;T;T;D

Sift4G

Benign

0.45

T;T;T;T;T;.;T;T;.

Polyphen

0.032

B;B;B;B;B;.;.;.;.

Vest4

0.14

MutPred

0.26

Gain of MoRF binding (P = 0.0093);Gain of MoRF binding (P = 0.0093);Gain of MoRF binding (P = 0.0093);Gain of MoRF binding (P = 0.0093);Gain of MoRF binding (P = 0.0093);Gain of MoRF binding (P = 0.0093);Gain of MoRF binding (P = 0.0093);Gain of MoRF binding (P = 0.0093);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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over