5-79115501-C-T

Position:

• chr5-79115501-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001713.3(BHMT):​c.34-266C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,770 control chromosomes in the GnomAD database, including 8,871 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8871 hom., cov: 31)
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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]

LOC124901012 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BHMT	NM_001713.3	c.34-266C>T		intron_variant		ENST00000274353.10	NP_001704.2
LOC124901012	XR_007058837.1	n.80-203G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BHMT	ENST00000274353.10	c.34-266C>T		intron_variant		1	NM_001713.3	ENSP00000274353	P1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49642 AN: 151652 Hom.: 8842 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0884

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.328 AC: 49714 AN: 151770 Hom.: 8871 Cov.: 31 AF XY: 0.322 AC XY: 23903 AN XY: 74194

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.0884

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.313

Alfa AF: 0.315 Hom.: 8235

Bravo AF: 0.332

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs7700970; hg19: chr5-78411324;