1-151847396-T-A

Position:

• chr1-151847396-T-A

Variant summary

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

The ENST00000368817.10(THEM5):​c.719A>T​(p.Gln240Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: THEM5 ENST00000368817.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.321

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:):

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=0.10720149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEM5	NM_182578.4	c.719A>T	p.Gln240Leu	missense_variant	6/6	ENST00000368817.10	NP_872384.2
THEM5	XM_011509421.2	c.594A>T	p.Ala198Ala	synonymous_variant	5/5		XP_011507723.1
C2CD4D-AS1	NR_024237.2	n.1031-2837T>A		intron_variant
C2CD4D-AS1	NR_152846.1	n.951-2837T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THEM5	ENST00000368817.10	c.719A>T	p.Gln240Leu	missense_variant	6/6	1	NM_182578.4	ENSP00000357807.4
THEM5	ENST00000453881.2	c.240A>T	p.Ala80Ala	synonymous_variant	3/3	4		ENSP00000406809.2
C2CD4D-AS1	ENST00000434182.1	n.354-2837T>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 11, 2022

The c.719A>T (p.Q240L) alteration is located in exon 6 (coding exon 6) of the THEM5 gene. This alteration results from a A to T substitution at nucleotide position 719, causing the glutamine (Q) at amino acid position 240 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.075
Sift	Benign	0.19	T
Sift4G	Benign	0.27	T
Polyphen		0.15	B
Vest4		0.32
MutPred		0.43		Loss of disorder (P = 0.0244);
MVP		0.21
MPC		0.077
ClinPred		0.20	T
GERP RS		-2.3
Varity_R		0.42
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-151819872;