15-78894883-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006791.4(MORF4L1):c.866A>G(p.Asn289Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000143 in 1,613,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: MORF4L1 NM_006791.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06543496).
• BS2: High AC in GnomAd at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MORF4L1	NM_006791.4	c.866A>G	p.Asn289Ser	missense_variant	11/12	ENST00000426013.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MORF4L1	ENST00000426013.7	c.866A>G	p.Asn289Ser	missense_variant	11/12	1	NM_006791.4	P1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000123 AC: 31 AN: 251448 Hom.: 0 AF XY: 0.000162 AC XY: 22 AN XY: 135900

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000142 AC: 207 AN: 1460782 Hom.: 0 Cov.: 29 AF XY: 0.000160 AC XY: 116 AN XY: 726830

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000529

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000126

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152358 Hom.: 0 Cov.: 32 AF XY: 0.000174 AC XY: 13 AN XY: 74504

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000140 Hom.: 0

Bravo AF: 0.000113

ExAC AF: 0.000173 AC: 21

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000356

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

Sep 07, 2022

The c.983A>G (p.N328S) alteration is located in exon 12 (coding exon 12) of the MORF4L1 gene. This alteration results from a A to G substitution at nucleotide position 983, causing the asparagine (N) at amino acid position 328 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	0.074
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	19
Dann	Benign	0.78
DEOGEN2	Benign	0.0065	T;.;T;.;.;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T;T;D;T;.;D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.065	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.97	D;D;D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.84	N;N;N;N;N;N
REVEL	Benign	0.069
Sift	Benign	0.69	T;T;T;T;T;T
Sift4G	Benign	0.87	T;T;T;T;T;T
Polyphen		0.0, 0.0010	.;B;B;.;.;.
Vest4		0.17
MVP		0.36
MPC		0.40
ClinPred		0.043	T
GERP RS		5.0
Varity_R		0.39
gMVP		0.099

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

Other links and lift over

dbSNP: rs186560594; hg19: chr15-79187225;