X-103676514-C-T

Variant names:

• chrX-103676514-C-T
• rs1402324697
• NM_012286.3:c.514G>A

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.514G>A​(p.Val172Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,208,803 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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 0.0000090 (0 hom., 0 hem., cov: 21)
  • Exomes 𝑓: 0.0000046 (0 hom. 0 hem.)
• Consequence: MORF4L2 NM_012286.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.772
• 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=0.0998033).

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.514G>A	p.Val172Ile	missense	Exon 4 of 4	NP_036418.1	Q15014
	MORF4L2	NM_001142418.2		c.514G>A	p.Val172Ile	missense	Exon 5 of 5	NP_001135890.1	Q15014
	MORF4L2	NM_001142419.2		c.514G>A	p.Val172Ile	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.514G>A	p.Val172Ile	missense	Exon 4 of 4	ENSP00000391969.2	Q15014
	MORF4L2	ENST00000360458.5	TSL:2	c.514G>A	p.Val172Ile	missense	Exon 4 of 4	ENSP00000353643.1	Q15014
	MORF4L2	ENST00000433176.6	TSL:2	c.514G>A	p.Val172Ile	missense	Exon 4 of 4	ENSP00000415476.2	Q15014

Frequencies

GnomAD3 genomes AF: 0.00000900 AC: 1 AN: 111083 Hom.: 0 Cov.: 21

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 182774 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000245

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000455 AC: 5 AN: 1097720 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363084

African (AFR) AF: 0.00 AC: 0 AN: 26386

American (AMR) AF: 0.00 AC: 0 AN: 35133

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19358

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 841899

Other (OTH) AF: 0.00 AC: 0 AN: 46074

GnomAD4 genome AF: 0.00000900 AC: 1 AN: 111083 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 33263

African (AFR) AF: 0.00 AC: 0 AN: 30530

American (AMR) AF: 0.00 AC: 0 AN: 10418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3516

South Asian (SAS) AF: 0.00 AC: 0 AN: 2634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53075

Other (OTH) AF: 0.00 AC: 0 AN: 1493

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000416

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	0.077
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	14
DANN	Uncertain	0.97
DEOGEN2	Benign	0.080	T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.77
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.019
Sift	Benign	0.068	T
Sift4G	Benign	0.082	T
Polyphen		0.26	B
Vest4		0.025
MVP		0.35
MPC		0.68
ClinPred		0.040	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.079
gMVP		0.14
Mutation Taster		=88/12	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: rs1402324697; hg19: chrX-102931442;