X-103676826-G-A

Variant names:

• chrX-103676826-G-A
• rs751380103
• NM_012286.3:c.202C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P68R) has been classified 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
• Publications: 0 publications found

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

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=0.18547982).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012286.3. 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
	MORF4L2	NM_012286.3	MANE Select	c.202C>T	p.Pro68Ser	missense	Exon 4 of 4	NP_036418.1	Q15014
	MORF4L2	NM_001142418.2		c.202C>T	p.Pro68Ser	missense	Exon 5 of 5	NP_001135890.1	Q15014
	MORF4L2	NM_001142419.2		c.202C>T	p.Pro68Ser	missense	Exon 4 of 4	NP_001135891.1	Q15014

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORF4L2	ENST00000441076.7	TSL:1 MANE Select	c.202C>T	p.Pro68Ser	missense	Exon 4 of 4	ENSP00000391969.2	Q15014
	MORF4L2	ENST00000360458.5	TSL:2	c.202C>T	p.Pro68Ser	missense	Exon 4 of 4	ENSP00000353643.1	Q15014
	MORF4L2	ENST00000433176.6	TSL:2	c.202C>T	p.Pro68Ser	missense	Exon 4 of 4	ENSP00000415476.2	Q15014

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 20

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	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
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.056
Sift	Benign	0.21	T
Sift4G	Benign	0.94	T
Polyphen		0.0020	B
Vest4		0.16
MutPred		0.34		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
Mutation Taster		=95/5	polymorphism

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

dbSNP: rs751380103; hg19: chrX-102931754;