X-103676220-G-A

Variant names:

• chrX-103676220-G-A
• NM_012286.3:c.808C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012286.3(MORF4L2):​c.808C>T​(p.Leu270Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,096,921 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000073 (0 hom. 1 hem.)
• Consequence: MORF4L2 NM_012286.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

Genes affected

MORF4L2 (HGNC:16849): (mortality factor 4 like 2) Predicted to be involved in heterochromatin assembly and histone modification. Predicted to act upstream of or within positive regulation of striated muscle cell differentiation and positive regulation of transcription by RNA polymerase II. Located in nucleolus; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40997615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORF4L2	NM_012286.3	c.808C>T	p.Leu270Phe	missense_variant	Exon 4 of 4	ENST00000441076.7	NP_036418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORF4L2	ENST00000441076.7	c.808C>T	p.Leu270Phe	missense_variant	Exon 4 of 4	1	NM_012286.3	ENSP00000391969.2
MORF4L2	ENST00000360458.5	c.808C>T	p.Leu270Phe	missense_variant	Exon 4 of 4	2		ENSP00000353643.1
MORF4L2	ENST00000433176.6	c.808C>T	p.Leu270Phe	missense_variant	Exon 4 of 4	2		ENSP00000415476.2
MORF4L2	ENST00000451301.5	c.808C>T	p.Leu270Phe	missense_variant	Exon 3 of 3	2		ENSP00000410532.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000729 AC: 8 AN: 1096921 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1 AN XY: 362307

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: 0.00000951

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.808C>T (p.L270F) alteration is located in exon 5 (coding exon 1) of the MORF4L2 gene. This alteration results from a C to T substitution at nucleotide position 808, causing the leucine (L) at amino acid position 270 to be replaced by a phenylalanine (F). 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	Uncertain	0.52
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;T;T;T;T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	.;.;D;.;.;D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.41	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;M;M;M;M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;.
REVEL	Benign	0.24
Sift	Benign	0.11	T;T;T;T;T;.
Sift4G	Benign	0.12	T;T;T;T;T;T
Polyphen		0.99	D;D;D;D;D;.
Vest4		0.30
MutPred		0.55		Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);.;
MVP		0.92
MPC		1.4
ClinPred		0.92	D
GERP RS		4.6
Varity_R		0.49
gMVP		0.80

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: chrX-102931148;