NM_000182.5:c.*510A>T

Variant names:

• chr2-26190740-T-A
• rs13432453
• NM_000182.5:c.*510A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000182.5(HADHA):​c.*510A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 200,956 control chromosomes in the GnomAD database, including 461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (451 hom., cov: 33)
  • Exomes 𝑓: 0.0058 (10 hom.)
• Consequence: HADHA NM_000182.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.563
• Publications: 1 publications found

Genes affected

HADHA (HGNC:4801): (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha) This gene encodes the alpha subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the alpha subunit catalyzing the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities. Mutations in this gene result in trifunctional protein deficiency or LCHAD deficiency. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation. [provided by RefSeq, Jul 2008]

GAREM2 (HGNC:27172): (GRB2 associated regulator of MAPK1 subtype 2)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-26190740-T-A is Benign according to our data. Variant chr2-26190740-T-A is described in ClinVar as Benign. ClinVar VariationId is 335363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000182.5. 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
	HADHA	NM_000182.5	MANE Select	c.*510A>T		3_prime_UTR	Exon 20 of 20	NP_000173.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HADHA	ENST00000380649.8	TSL:1 MANE Select	c.*510A>T		3_prime_UTR	Exon 20 of 20	ENSP00000370023.3	P40939-1
	HADHA	ENST00000492433.2	TSL:2	c.*510A>T		3_prime_UTR	Exon 19 of 19	ENSP00000438039.2	H0YFD6
	HADHA	ENST00000859324.1		c.*510A>T		3_prime_UTR	Exon 20 of 20	ENSP00000529383.1

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6401 AN: 152170 Hom.: 449 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0339

GnomAD4 exome AF: 0.00584 AC: 284 AN: 48668 Hom.: 10 Cov.: 0 AF XY: 0.00520 AC XY: 130 AN XY: 24990

African (AFR) AF: 0.139 AC: 183 AN: 1320

American (AMR) AF: 0.0115 AC: 42 AN: 3640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 924

East Asian (EAS) AF: 0.00 AC: 0 AN: 2976

South Asian (SAS) AF: 0.00618 AC: 35 AN: 5666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 160

European-Non Finnish (NFE) AF: 0.000271 AC: 8 AN: 29532

Other (OTH) AF: 0.00625 AC: 16 AN: 2558

GnomAD4 genome AF: 0.0421 AC: 6418 AN: 152288 Hom.: 451 Cov.: 33 AF XY: 0.0411 AC XY: 3062 AN XY: 74482

African (AFR) AF: 0.144 AC: 5960 AN: 41520

American (AMR) AF: 0.0208 AC: 318 AN: 15300

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

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

South Asian (SAS) AF: 0.00621 AC: 30 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68030

Other (OTH) AF: 0.0336 AC: 71 AN: 2114

Alfa AF: 0.0335 Hom.: 25

Bravo AF: 0.0491

Asia WGS AF: 0.0110 AC: 42 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (1)
-	-	1	Mitochondrial trifunctional protein deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.85
DANN	Benign	0.48
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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: rs13432453; hg19: chr2-26413609;