X-103676826-G-A

Position:

• chrX-103676826-G-A

Variant summary

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

The NM_012286.3(MORF4L2):​c.202C>T​(p.Pro68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: MORF4L2 NM_012286.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18547982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORF4L2	NM_012286.3	c.202C>T	p.Pro68Ser	missense_variant	4/4	ENST00000441076.7	NP_036418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORF4L2	ENST00000441076.7	c.202C>T	p.Pro68Ser	missense_variant	4/4	1	NM_012286.3	ENSP00000391969	P1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 20

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

Feb 28, 2023

The c.202C>T (p.P68S) 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 202, causing the proline (P) at amino acid position 68 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	0.064
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.083	T;T;T;T;T;.;.;.
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.67	.;.;T;.;.;.;T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;N;N;.;.;.
MutationTaster	Benign	1.0	D;N;N;N;N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.36	N;N;N;N;N;N;N;N
REVEL	Benign	0.056
Sift	Benign	0.21	T;T;T;T;T;T;T;T
Sift4G	Benign	0.94	T;T;T;T;T;.;T;T
Polyphen		0.0020	B;B;B;B;B;.;.;.
Vest4		0.16
MutPred		0.34		Gain of phosphorylation at P68 (P = 0.0187);Gain of phosphorylation at P68 (P = 0.0187);Gain of phosphorylation at P68 (P = 0.0187);Gain of phosphorylation at P68 (P = 0.0187);Gain of phosphorylation at P68 (P = 0.0187);Gain of phosphorylation at P68 (P = 0.0187);Gain of phosphorylation at P68 (P = 0.0187);Gain of phosphorylation at P68 (P = 0.0187);
MVP		0.71
ClinPred		0.24	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.048
gMVP		0.29

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-102931754;