3-53823776-A-T

Variant names:

• chr3-53823776-A-T
• rs12676
• NM_018397.5:c.233T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018397.5(CHDH):​c.233T>A​(p.Leu78His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 36)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHDH NM_018397.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 66 publications found

Genes affected

CHDH (HGNC:24288): (choline dehydrogenase) The protein encoded by this gene is a choline dehydrogenase that localizes to the mitochondrion. Variations in this gene can affect susceptibility to choline deficiency. A few transcript variants have been found for this gene, but the full-length nature of only one has been characterized to date. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05758679).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018397.5. 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
	CHDH	NM_018397.5	MANE Select	c.233T>A	p.Leu78His	missense	Exon 3 of 9	NP_060867.2	Q8NE62

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHDH	ENST00000315251.11	TSL:1 MANE Select	c.233T>A	p.Leu78His	missense	Exon 3 of 9	ENSP00000319851.5	Q8NE62
	CHDH	ENST00000875879.1		c.233T>A	p.Leu78His	missense	Exon 3 of 9	ENSP00000545938.1
	CHDH	ENST00000875888.1		c.233T>A	p.Leu78His	missense	Exon 3 of 9	ENSP00000545947.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152102 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 176366 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000141 AC: 2 AN: 1416162 Hom.: 0 Cov.: 90 AF XY: 0.00 AC XY: 0 AN XY: 701014

African (AFR) AF: 0.00 AC: 0 AN: 32338

American (AMR) AF: 0.00 AC: 0 AN: 38708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25350

East Asian (EAS) AF: 0.0000272 AC: 1 AN: 36810

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091430

Other (OTH) AF: 0.00 AC: 0 AN: 58640

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152102 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 74296

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 17754

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.15
DANN	Benign	0.31
DEOGEN2	Benign	0.16	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.013	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	N
PhyloP100		-0.27
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.67	N
REVEL	Benign	0.099
Sift	Benign	0.54	T
Sift4G	Benign	0.61	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.43		Gain of disorder (P = 0.0185)
MVP		0.29
MPC		0.35
ClinPred		0.065	T
GERP RS		-12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.47
Mutation Taster		=95/5	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: rs12676; hg19: chr3-53857803;