15-78873045-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006791.4(MORF4L1):c.28A>G(p.Lys10Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MORF4L1 NM_006791.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.80

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20255083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MORF4L1	NM_006791.4	c.28A>G	p.Lys10Glu	missense_variant	1/12	ENST00000426013.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MORF4L1	ENST00000426013.7	c.28A>G	p.Lys10Glu	missense_variant	1/12	1	NM_006791.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.28A>G (p.K10E) alteration is located in exon 1 (coding exon 1) of the MORF4L1 gene. This alteration results from a A to G substitution at nucleotide position 28, causing the lysine (K) at amino acid position 10 to be replaced by a glutamic acid (E). 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	Pathogenic	0.86
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
Cadd	Uncertain	23
Dann	Uncertain	0.99
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.058
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.27
MutPred		0.32		Loss of methylation at K10 (P = 2e-04);Loss of methylation at K10 (P = 2e-04);Loss of methylation at K10 (P = 2e-04);
MVP		0.87
MPC		0.82
ClinPred		0.87	D
GERP RS		4.5
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.62
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-79165387;