X-103676772-C-T

Variant names:

• chrX-103676772-C-T
• rs1486240356
• NM_012286.3:c.256G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_012286.3(MORF4L2):​c.256G>A​(p.Gly86Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,202,580 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000096 (0 hom., 0 hem., cov: 20)
  • Exomes 𝑓: 0.000015 (0 hom. 6 hem.)
• Consequence: MORF4L2 NM_012286.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3554477).
• BS2: High Hemizygotes in GnomAdExome4 at 6 gene

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.256G>A	p.Gly86Arg	missense	Exon 4 of 4	NP_036418.1	Q15014
	MORF4L2	NM_001142418.2		c.256G>A	p.Gly86Arg	missense	Exon 5 of 5	NP_001135890.1	Q15014
	MORF4L2	NM_001142419.2		c.256G>A	p.Gly86Arg	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.256G>A	p.Gly86Arg	missense	Exon 4 of 4	ENSP00000391969.2	Q15014
	MORF4L2	ENST00000360458.5	TSL:2	c.256G>A	p.Gly86Arg	missense	Exon 4 of 4	ENSP00000353643.1	Q15014
	MORF4L2	ENST00000433176.6	TSL:2	c.256G>A	p.Gly86Arg	missense	Exon 4 of 4	ENSP00000415476.2	Q15014

Frequencies

GnomAD3 genomes AF: 0.00000955 AC: 1 AN: 104678 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000194

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000155 AC: 17 AN: 1097902 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 6 AN XY: 363274

African (AFR) AF: 0.00 AC: 0 AN: 26396

American (AMR) AF: 0.00 AC: 0 AN: 35169

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54099

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4111

European-Non Finnish (NFE) AF: 0.0000202 AC: 17 AN: 842048

Other (OTH) AF: 0.00 AC: 0 AN: 46081

GnomAD4 genome AF: 0.00000955 AC: 1 AN: 104678 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 27270

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28585

American (AMR) AF: 0.00 AC: 0 AN: 9353

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2569

East Asian (EAS) AF: 0.00 AC: 0 AN: 3276

South Asian (SAS) AF: 0.00 AC: 0 AN: 2188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5019

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.0000194 AC: 1 AN: 51420

Other (OTH) AF: 0.00 AC: 0 AN: 1375

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	Uncertain	0.35
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.4
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.14
Sift	Uncertain	0.011	D
Sift4G	Benign	0.59	T
Polyphen		0.013	B
Vest4		0.31
MutPred		0.39		Gain of solvent accessibility (P = 0.0097)
MVP		0.67
MPC		1.0
ClinPred		0.69	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.81
Mutation Taster		=83/17	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: rs1486240356; hg19: chrX-102931700;