chr5-163516577-G-A

Variant names:

• chr5-163516577-G-A
• rs201528924
• NM_013283.5:c.586G>A

Variant summary

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

The NM_013283.5(MAT2B):​c.586G>A​(p.Ala196Thr) variant causes a missense change. 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. A196P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAT2B NM_013283.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03
• Publications: 1 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: 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_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.586G>A	p.Ala196Thr	missense	Exon 5 of 7	NP_037415.1	A0A140VJP2
	MAT2B	NM_182796.2		c.553G>A	p.Ala185Thr	missense	Exon 5 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.586G>A	p.Ala196Thr	missense	Exon 5 of 7	ENSP00000325425.6	Q9NZL9-1
	MAT2B	ENST00000280969.9	TSL:1	c.553G>A	p.Ala185Thr	missense	Exon 5 of 7	ENSP00000280969.5	Q9NZL9-2
	MAT2B	ENST00000518095.5	TSL:1	c.586G>A	p.Ala196Thr	missense	Exon 5 of 5	ENSP00000428046.1	Q9NZL9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.0
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.55		Gain of ubiquitination at K191 (P = 0.0645)
MVP		0.56
MPC		1.1
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.93
gMVP		0.59
Mutation Taster		=13/87	disease causing

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: rs201528924; hg19: chr5-162943583;