5-163518263-C-G

Variant names:

• chr5-163518263-C-G
• rs80145956
• NM_013283.5:c.905C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013283.5(MAT2B):​c.905C>G​(p.Thr302Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. 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. T302I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAT2B NM_013283.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870
• Publications: 10 publications found

Genes affected

MAT2B (HGNC:6905): (methionine adenosyltransferase 2 non-catalytic beta subunit) The protein encoded by this gene belongs to the methionine adenosyltransferase (MAT) family. MAT catalyzes the biosynthesis of S-adenosylmethionine from methionine and ATP. This protein is the regulatory beta subunit of MAT. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06766859).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013283.5. 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
	MAT2B	NM_013283.5	MANE Select	c.905C>G	p.Thr302Ser	missense	Exon 7 of 7	NP_037415.1	A0A140VJP2
	MAT2B	NM_182796.2		c.872C>G	p.Thr291Ser	missense	Exon 7 of 7	NP_877725.1	Q9NZL9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2B	ENST00000321757.11	TSL:1 MANE Select	c.905C>G	p.Thr302Ser	missense	Exon 7 of 7	ENSP00000325425.6	Q9NZL9-1
	MAT2B	ENST00000280969.9	TSL:1	c.872C>G	p.Thr291Ser	missense	Exon 7 of 7	ENSP00000280969.5	Q9NZL9-2
	MAT2B	ENST00000518095.5	TSL:1	c.*1492C>G		3_prime_UTR	Exon 5 of 5	ENSP00000428046.1	Q9NZL9-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N
PhyloP100		0.87
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.082
Sift	Benign	0.76	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.046
MutPred		0.32		Gain of ubiquitination at K299 (P = 0.0469)
MVP		0.29
MPC		0.32
ClinPred		0.075	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.29
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: rs80145956; hg19: chr5-162945269;