chr1-151847780-C-A

Variant names:

• chr1-151847780-C-A
• NM_182578.4:c.658G>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.658G>T​(p.Ala220Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A220T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: THEM5 NM_182578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720

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=0.21591496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THEM5	NM_182578.4	c.658G>T	p.Ala220Ser	missense_variant	Exon 5 of 6	ENST00000368817.10	NP_872384.2
THEM5	XM_011509421.2	c.576-366G>T		intron_variant	Intron 4 of 4		XP_011507723.1
C2CD4D-AS1	NR_024237.2	n.1031-2453C>A		intron_variant	Intron 4 of 4
C2CD4D-AS1	NR_152846.1	n.951-2453C>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THEM5	ENST00000368817.10	c.658G>T	p.Ala220Ser	missense_variant	Exon 5 of 6	1	NM_182578.4	ENSP00000357807.4
THEM5	ENST00000453881.2	c.222-366G>T		intron_variant	Intron 2 of 2	4		ENSP00000406809.2
C2CD4D-AS1	ENST00000434182.1	n.354-2453C>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461822 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.3
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.047	D
Polyphen		0.91	P
Vest4		0.38
MutPred		0.49		Gain of disorder (P = 0.0278);
MVP		0.17
MPC		0.30
ClinPred		0.66	D
GERP RS		-7.6
Varity_R		0.59
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-151820256;