chr1-151847828-C-A

Variant names:

• chr1-151847828-C-A
• rs200948412
• NM_182578.4:c.610G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182578.4(THEM5):​c.610G>T​(p.Val204Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V204I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: THEM5 NM_182578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

Genes affected

THEM5 (HGNC:26755): (thioesterase superfamily member 5) Enables palmitoyl-CoA hydrolase activity. Involved in long-chain fatty-acyl-CoA metabolic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

C2CD4D-AS1 (HGNC:54045): (C2CD4D and THEM5 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06930256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THEM5	NM_182578.4	c.610G>T	p.Val204Leu	missense_variant	Exon 5 of 6	ENST00000368817.10	NP_872384.2
THEM5	XM_011509421.2	c.575+354G>T		intron_variant	Intron 4 of 4		XP_011507723.1
C2CD4D-AS1	NR_024237.2	n.1031-2405C>A		intron_variant	Intron 4 of 4
C2CD4D-AS1	NR_152846.1	n.951-2405C>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THEM5	ENST00000368817.10	c.610G>T	p.Val204Leu	missense_variant	Exon 5 of 6	1	NM_182578.4	ENSP00000357807.4
THEM5	ENST00000453881.2	c.221+354G>T		intron_variant	Intron 2 of 2	4		ENSP00000406809.2
C2CD4D-AS1	ENST00000434182.1	n.354-2405C>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251432 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135904

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 SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461854 Hom.: 0 Cov.: 67 AF XY: 0.00000275 AC XY: 2 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.39
DANN	Benign	0.53
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.035
Sift	Benign	0.30	T
Sift4G	Benign	0.28	T
Polyphen		0.010	B
Vest4		0.17
MutPred		0.56		Loss of catalytic residue at V204 (P = 0.0769);
MVP		0.18
MPC		0.079
ClinPred		0.062	T
GERP RS		-1.4
Varity_R		0.28
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs200948412; hg19: chr1-151820304;