chr15-78873045-A-G

Variant names:

• chr15-78873045-A-G
• NM_006791.4:c.28A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001265603.2(MORF4L1):​c.-122A>G variant causes a 5 prime UTR premature start codon gain 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_001265603.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.80
• Publications: 0 publications found

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

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=0.20255083).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001265603.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORF4L1	NM_006791.4	MANE Select	c.28A>G	p.Lys10Glu	missense	Exon 1 of 12	NP_006782.1	Q9UBU8-2
	MORF4L1	NM_001265603.2		c.-122A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001252532.1	Q9UBU8-3
	MORF4L1	NM_001265604.2		c.-398A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001252533.1	Q9UBU8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORF4L1	ENST00000426013.7	TSL:1 MANE Select	c.28A>G	p.Lys10Glu	missense	Exon 1 of 12	ENSP00000408880.2	Q9UBU8-2
	MORF4L1	ENST00000331268.9	TSL:1	c.28A>G	p.Lys10Glu	missense	Exon 1 of 13	ENSP00000331310.5	Q9UBU8-1
	MORF4L1	ENST00000558893.5	TSL:1	n.73A>G		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.058
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.25
Sift	Benign	0.11	T
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.27
MutPred		0.32		Loss of methylation at K10 (P = 2e-04)
MVP		0.87
MPC		0.82
ClinPred		0.87	D
GERP RS		4.5
PromoterAI		0.050	Neutral
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

Other links and lift over

hg19: chr15-79165387;