2-197540370-C-G

Variant names:

• chr2-197540370-C-G
• rs201150302
• NM_015387.5:c.287C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015387.5(MOB4):​c.287C>G​(p.Thr96Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T96I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOB4 NM_015387.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.83
• Publications: 0 publications found

Genes affected

MOB4 (HGNC:17261): (MOB family member 4, phocein) This gene was identified based on its similarity with the mouse counterpart. Studies of the mouse counterpart suggest that the expression of this gene may be regulated during oocyte maturation and preimplantation following zygotic gene activation. Alternatively spliced transcript variants encoding distinct isoforms have been observed. Naturally occurring read-through transcription occurs between this locus and the neighboring locus HSPE1.[provided by RefSeq, Feb 2011]

HSPE1-MOB4 (HGNC:49184): (HSPE1-MOB4 readthrough) This locus represents naturally occurring read-through transcription between the neighboring HSPE1 (heat shock 10kDa protein 1 (chaperonin 10)) and MOB4 (MOB family member 4, phocein) genes on chromosome 2. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015387.5. 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
	MOB4	NM_015387.5	MANE Select	c.287C>G	p.Thr96Ser	missense	Exon 5 of 8	NP_056202.2
	HSPE1-MOB4	NM_001202485.2		c.395C>G	p.Thr132Ser	missense	Exon 6 of 9	NP_001189414.1	S4R3N1
	MOB4	NM_001100819.3		c.224C>G	p.Thr75Ser	missense	Exon 4 of 7	NP_001094289.1	Q9Y3A3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOB4	ENST00000323303.9	TSL:1 MANE Select	c.287C>G	p.Thr96Ser	missense	Exon 5 of 8	ENSP00000315702.4	Q9Y3A3-1
	HSPE1-MOB4	ENST00000604458.1	TSL:3	c.395C>G	p.Thr132Ser	missense	Exon 6 of 9	ENSP00000474534.1	S4R3N1
	MOB4	ENST00000233892.8	TSL:1	c.191C>G	p.Thr64Ser	missense	Exon 5 of 8	ENSP00000233892.4	Q9Y3A3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0090	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.94	L
PhyloP100		7.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.18
Sift	Benign	0.22	T
Sift4G	Benign	0.45	T
Polyphen		0.088	B
Vest4		0.67
MutPred		0.79		Gain of disorder (P = 0.0458)
MVP		0.082
MPC		1.0
ClinPred		0.65	D
GERP RS		5.6
Varity_R		0.51
gMVP		0.55
Mutation Taster		=181/119	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201150302; hg19: chr2-198405094;