rs542592055

Variant names:

• chr5-79121300-T-G
• rs542592055
• NM_001713.3:c.560T>G
• BHMT p.Ile187Ser

Your query was ambiguous. Multiple possible variants found:

• chr5-79121300-T-G
• chr5-79121300-T-C

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+1 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 1 classification points (ACGS-UK Somatic Oncogenicity v2025). O6_Supporting

The NM_001713.3(BHMT):c.560T>G (p.Ile187Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000985 (AC=159) in the gnomAD database across 1,614,092 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.000159. In-silico predictor (REVEL) classifies this variant as likely damaging/oncogenic. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 7.64). Variant has been reported in ClinVar as Uncertain Significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000097 (0 hom.)
• Consequence: BHMT NM_001713.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.64
• Publications: 1 publications found

Genes affected

BHMT (HGNC:1047): (betaine--homocysteine S-methyltransferase) This gene encodes a cytosolic enzyme that catalyzes the conversion of betaine and homocysteine to dimethylglycine and methionine, respectively. Defects in this gene could lead to hyperhomocyst(e)inemia, but such a defect has not yet been observed. [provided by RefSeq, Jul 2008]

DMGDH (HGNC:24475): (dimethylglycine dehydrogenase) This gene encodes an enzyme involved in the catabolism of choline, catalyzing the oxidative demethylation of dimethylglycine to form sarcosine. The enzyme is found as a monomer in the mitochondrial matrix, and uses flavin adenine dinucleotide and folate as cofactors. Mutation in this gene causes dimethylglycine dehydrogenase deficiency, characterized by a fishlike body odor, chronic muscle fatigue, and elevated levels of the muscle form of creatine kinase in serum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

DMGDH Gene-Disease associations (from GenCC):

• dimethylglycine dehydrogenase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O6Computational evidence supports deleterious effect		Computational evidence supports a deleterious/oncogenic effect; Missense variant — primary computational scorer supports an oncogenic/deleterious effect

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001713.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	BHMT NM_001713.3	MANE Select	c.560T>G p.Ile187Ser	missense	Exon 5 of 8	Prot: NP_001704.2 UniProt:

BHMT NM_001713.3

MANE Select

HGVSc / HGVSpc.560T>Gp.Ile187Ser

Exon rankExon 5 of 8

missense

Prot: NP_001704.2UniProt: Q93088

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	BHMT ENST00000274353.10	TSL:1MANE Select	c.560T>G p.Ile187Ser	missense	Exon 5 of 8	Prot: ENSP00000274353.5 UniProt:
	BHMT ENST00000910530.1		c.560T>G p.Ile187Ser	missense	Exon 5 of 8	Prot: ENSP00000580589.1 UniProt:
	BHMT ENST00000910525.1		c.560T>G p.Ile187Ser	missense	Exon 5 of 8	Prot: ENSP00000580584.1 UniProt:

BHMT ENST00000274353.10

TSL:1MANE Select

HGVSc / HGVSpc.560T>Gp.Ile187Ser

Exon rankExon 5 of 8

missense

Prot: ENSP00000274353.5UniProt: Q93088

BHMT ENST00000910530.1

HGVSc / HGVSpc.560T>Gp.Ile187Ser

Exon rankExon 5 of 8

missense

Prot: ENSP00000580589.1UniProt: A0ACI8SI12

BHMT ENST00000910525.1

HGVSc / HGVSpc.560T>Gp.Ile187Ser

Exon rankExon 5 of 8

missense

Prot: ENSP00000580584.1UniProt: A0ACI8SHS3

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.000112	AC:17	Hom:0	AN:152220	Cov:31
GnomAD2 exomes	AF: 0.0000636	AC:16	Hom:	AN:251494	Cov:
GnomAD4 exome	AF: 0.0000971	AC:142	Hom:0	AN:1461872	Cov:33
GnomAD4 genome	AF: 0.000112	AC:17	Hom:0	AN:152220	Cov:31
TOPMed (Bravo)	AF: 0.0000907	AC:24	Hom:0	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.0000937	AC:4	Hom:0	AN:42692	Cov:
Local & regional cohorts 2 sources Population-specific and national genomic databases
Denmark Genome	AF: 0.00333	AC:1	Hom:	AN:300	Cov:
Turkish Variome	AF: 0.000647	AC:1	Hom:0	AN:1546	Cov:

Showing 8 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.000540 *	6	11110	0.000170 *	3	17614
BipEx(Bipolar disorder (including schizoaffective))	0.0000704	2	28420	0.000173	5	28844
Epi25(Epilepsy)	0.000119	5	41958	0.000135	9	66884
SCHEMA(Schizophrenia)	0.0000265	3	113104	0.0000787	15	190560

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Pathogenic	27
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	1.0	D
FuncVEP CTI	Pathogenic	0.75
GPN-Star LLR	N/A	-10
GPN-Star score	N/A	10
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.71	T
Mutation Taster	N/A	20/80	disease causing
MutationAssessor	Uncertain	2.8	M
PhyloP100	Pathogenic	7.6
popEVE	Benign	-3.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.3	D
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.2e-153
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Varity_R	N/A	0.91
VESM-3B	Benign	-13

Showing 30 of 30 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs542592055;

hg19: chr5-78417123;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar