chr5-79121272-GGT-TCG

Variant names:

• chr5-79121272-GGT-TCG
• NM_001713.3:c.532_534delGGTinsTCG
• BHMT p.Gly178Ser

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_001713.3(BHMT):c.532_534delGGTinsTCG (p.Gly178Ser) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 9.60). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.G178C: Uncertain_significance (ClinVar VariationId 3480583, 1 star)

• Frequency: Genomes: not found (cov: 31)
• Consequence: BHMT NM_001713.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60
• Publications: 0 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 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

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.532_534delGGTinsTCG p.Gly178Ser	missense	N/A	Prot: NP_001704.2 UniProt:

BHMT NM_001713.3

MANE Select

HGVSc / HGVSpc.532_534delGGTinsTCGp.Gly178Ser

Exon rankN/A

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.532_534delGGTinsTCG p.Gly178Ser	missense	N/A	Prot: ENSP00000274353.5 UniProt:
	BHMT ENST00000910530.1		c.532_534delGGTinsTCG p.Gly178Ser	missense	N/A	Prot: ENSP00000580589.1 UniProt:
	BHMT ENST00000910525.1		c.532_534delGGTinsTCG p.Gly178Ser	missense	N/A	Prot: ENSP00000580584.1 UniProt:

BHMT ENST00000274353.10

TSL:1MANE Select

HGVSc / HGVSpc.532_534delGGTinsTCGp.Gly178Ser

Exon rankN/A

missense

Prot: ENSP00000274353.5UniProt: Q93088

BHMT ENST00000910530.1

HGVSc / HGVSpc.532_534delGGTinsTCGp.Gly178Ser

Exon rankN/A

missense

Prot: ENSP00000580589.1UniProt: A0ACI8SI12

BHMT ENST00000910525.1

HGVSc / HGVSpc.532_534delGGTinsTCGp.Gly178Ser

Exon rankN/A

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 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Pathogenic	9.6

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

hg19: chr5-78417095;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

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