chr8-142727653-T-A

Position:

• chr8-142727653-T-A

Variant summary

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

The ENST00000336138.4(THEM6):​c.307T>A​(p.Ser103Thr) 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: THEM6 ENST00000336138.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.643

Genes affected

THEM6 (HGNC:29656): (thioesterase superfamily member 6) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253806 (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=0.08415833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEM6	NM_016647.3	c.307T>A	p.Ser103Thr	missense_variant	1/2	ENST00000336138.4	NP_057731.1
THEM6	NM_001363000.2	c.307T>A	p.Ser103Thr	missense_variant	1/2		NP_001349929.1
THEM6	NR_156431.2	n.431T>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THEM6	ENST00000336138.4	c.307T>A	p.Ser103Thr	missense_variant	1/2	1	NM_016647.3	ENSP00000338607.3
ENSG00000253806	ENST00000519782.1	n.38A>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1293586 Hom.: 0 Cov.: 63 AF XY: 0.00 AC XY: 0 AN XY: 634804

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

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

May 26, 2024

The c.307T>A (p.S103T) alteration is located in exon 1 (coding exon 1) of the THEM6 gene. This alteration results from a T to A substitution at nucleotide position 307, causing the serine (S) at amino acid position 103 to be replaced by a threonine (T). 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	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.43	N
MutationTaster	Benign	0.95	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.023
Sift	Benign	0.60	T
Sift4G	Benign	0.62	T
Polyphen		0.48	P
Vest4		0.10
MutPred		0.38		Loss of helix (P = 0.079);
MVP		0.12
MPC		1.1
ClinPred		0.17	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.27
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr8-143809071;