Genetic Variant MORF4L2:p.Asn117Ser (chrX-103676678-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012286.3(MORF4L2):c.350A>G(p.Asn117Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000306 in 1,206,411 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 121 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 0.00029 ( 0 hom., 7 hem., cov: 21)

Exomes 𝑓: 0.00031 ( 0 hom. 114 hem. )

Consequence

MORF4L2
NM_012286.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03278917).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORF4L2	NM_012286.3 link	c.350A>G	p.Asn117Ser	missense_variant	Exon 4 of 4	ENST00000441076.7	NP_036418.1	Q15014

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORF4L2	ENST00000441076.7 link	c.350A>G	p.Asn117Ser	missense_variant	Exon 4 of 4	1	NM_012286.3	ENSP00000391969.2		Q15014

Frequencies

GnomAD3 genomes

AF:

0.000286

AC:

AN:

108297

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

30593

show subpopulations

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000101

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:

0.000515

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000241

AC:

AN:

182763

Hom.:

AF XY:

0.000267

AC XY:

AN XY:

67419

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:

0.000539

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000308

AC:

338

AN:

1098053

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

114

AN XY:

363409

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000380

Gnomad4 OTH exome

AF:

0.000304

GnomAD4 genome

AF:

0.000286

AC:

AN:

108358

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

30664

show subpopulations

Gnomad4 AFR

AF:

0.000101

Gnomad4 AMR

AF:

0.000101

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000428

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.350A>G (p.N117S) alteration is located in exon 5 (coding exon 1) of the MORF4L2 gene. This alteration results from a A to G substitution at nucleotide position 350, causing the asparagine (N) at amino acid position 117 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.054

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

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

.;.;D;.;.;D;.;D;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.033

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

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;L;L;L;L;.;.;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.55

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

REVEL

Benign

0.095

Sift

Benign

0.85

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

Sift4G

Benign

1.0

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

Polyphen

0.0050

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

Vest4

0.18

MVP

0.77

MPC

0.69

ClinPred

0.048

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.080

gMVP

0.59

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