Variant 15-78891513-A-G 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_006791.4(MORF4L1):c.379A>G(p.Ser127Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000039 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

MORF4L1
NM_006791.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.67

Variant links:

Genes affected

MORF4L1 (HGNC:16989): (mortality factor 4 like 1) Enables protein N-terminus binding activity. Involved in double-strand break repair via homologous recombination and histone modification. Located in nuclear speck. Part of NuA4 histone acetyltransferase complex and Sin3 complex. [provided by Alliance of Genome Resources, Apr 2022]

MORF4L1 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=0.16384083).

BS2

High AC in GnomAdExome at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MORF4L1	NM_006791.4 linkuse as main transcript	c.379A>G	p.Ser127Gly	missense_variant	7/12	ENST00000426013.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MORF4L1	ENST00000426013.7 linkuse as main transcript	c.379A>G	p.Ser127Gly	missense_variant	7/12	1	NM_006791.4	P1	Q9UBU8-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152196

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251422

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135880

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:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727214

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:

0.0000374

Gnomad4 NFE exome

AF:

0.0000522

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Oct 26, 2022

The c.496A>G (p.S166G) alteration is located in exon 8 (coding exon 8) of the MORF4L1 gene. This alteration results from a A to G substitution at nucleotide position 496, causing the serine (S) at amino acid position 166 to be replaced by a glycine (G). 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

0.072

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.023

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

Eigen

Benign

-0.15

Eigen_PC

Benign

0.057

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

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

M_CAP

Benign

0.0043

MetaRNN

Benign

0.16

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

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.93

D;D;D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.3

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

REVEL

Benign

0.056

Sift

Benign

0.12

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

Sift4G

Benign

0.12

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

Polyphen

0.0010, 0.011

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

Vest4

0.25

MutPred

0.29

.;.;Loss of phosphorylation at S166 (P = 0.0073);.;.;.;.;.;.;.;.;.;

MVP

0.45

MPC

0.49

ClinPred

0.22

GERP RS

4.9

Varity_R

0.24

gMVP

0.27

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