rs376291639

Variant names:

• chr15-78891502-G-A
• NM_006791.4:c.368G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-78891502-G-A
• chr15-78891502-G-C

Variant summary

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

The NM_006791.4(MORF4L1):​c.368G>A​(p.Gly123Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G123A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MORF4L1 NM_006791.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.04

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORF4L1	NM_006791.4	c.368G>A	p.Gly123Asp	missense_variant	Exon 7 of 12	ENST00000426013.7	NP_006782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORF4L1	ENST00000426013.7	c.368G>A	p.Gly123Asp	missense_variant	Exon 7 of 12	1	NM_006791.4	ENSP00000408880.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461720 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727166

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: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;.;T;T;.;.;.;.;.;T;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.79	T;T;T;T;T;T;.;T;T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.50	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;.;M;.;.;.;.;.;.;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.3	N;N;N;D;N;D;N;N;D;D;N;D
REVEL	Benign	0.21
Sift	Benign	0.11	T;T;T;D;T;T;T;T;T;T;T;D
Sift4G	Benign	0.20	T;T;T;D;T;T;T;T;T;T;T;D
Polyphen		0.98, 0.97	.;D;D;.;.;.;.;.;.;.;.;.
Vest4		0.69
MutPred		0.37		.;.;Loss of MoRF binding (P = 0.0663);.;.;.;.;.;.;.;.;.;
MVP		0.49
MPC		1.4
ClinPred		0.97	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.50
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-79183844;