chr5-163518329-T-C

Variant names:

• chr5-163518329-T-C
• rs192771488
• NM_013283.5:c.971T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_013283.5(MAT2B):​c.971T>C​(p.Ile324Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,214 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (3 hom.)
• Consequence: MAT2B NM_013283.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0085347).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.971T>C	p.Ile324Thr	missense	Exon 7 of 7	NP_037415.1	A0A140VJP2
	MAT2B	NM_182796.2		c.938T>C	p.Ile313Thr	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.971T>C	p.Ile324Thr	missense	Exon 7 of 7	ENSP00000325425.6	Q9NZL9-1
	MAT2B	ENST00000280969.9	TSL:1	c.938T>C	p.Ile313Thr	missense	Exon 7 of 7	ENSP00000280969.5	Q9NZL9-2
	MAT2B	ENST00000518095.5	TSL:1	c.*1558T>C		3_prime_UTR	Exon 5 of 5	ENSP00000428046.1	Q9NZL9-3

Frequencies

GnomAD3 genomes AF: 0.000461 AC: 70 AN: 151994 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000540 AC: 135 AN: 250214 AF XY: 0.000525

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000873

Gnomad ASJ exome AF: 0.00868

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000821

GnomAD4 exome AF: 0.000253 AC: 370 AN: 1461120 Hom.: 3 Cov.: 30 AF XY: 0.000261 AC XY: 190 AN XY: 726858

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.000762 AC: 34 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00912 AC: 238 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000540 AC: 60 AN: 1111666

Other (OTH) AF: 0.000613 AC: 37 AN: 60344

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152094 Hom.: 1 Cov.: 32 AF XY: 0.000552 AC XY: 41 AN XY: 74332

African (AFR) AF: 0.0000482 AC: 2 AN: 41526

American (AMR) AF: 0.00229 AC: 35 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 29 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67984

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000881 Hom.: 2

Bravo AF: 0.000506

ExAC AF: 0.000371 AC: 45

EpiCase AF: 0.000109

EpiControl AF: 0.000238

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	0.088
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.067
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.0085	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.4
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.034
Sift	Benign	0.42	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.19
MVP		0.50
MPC		0.45
ClinPred		0.033	T
GERP RS		5.9
Varity_R		0.17
gMVP		0.29
Mutation Taster		=72/28	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: rs192771488; hg19: chr5-162945335;