chr11-78064087-A-T

Position:

• chr11-78064087-A-T

Variant summary

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

The NM_003251.4(THRSP):​c.206A>T​(p.Asp69Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: THRSP NM_003251.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.279

Genes affected

THRSP (HGNC:11800): (thyroid hormone responsive) The protein encoded by this gene is similar to the gene product of S14, a rat gene whose expression is limited to liver and adipose tissue and is controlled by nutritional and hormonal factors. This gene has been shown to be expressed in liver and adipocytes, particularly in lipomatous modules. It is also found to be expressed in lipogenic breast cancers, which suggests a role in controlling tumor lipid metabolism. [provided by RefSeq, Jul 2008]

NDUFC2-KCTD14 (HGNC:42956): (NDUFC2-KCTD14 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NDUFC2 (NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2, 14.5kDa) and KCTD14 (potassium channel tetramerisation domain containing 14) genes on chromosome 11. The read-through transcripts share sequence identity with the upstream gene product and one variant has a frameshifted C-terminal region derived from the downstream gene exons. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THRSP	NM_003251.4	c.206A>T	p.Asp69Val	missense_variant	1/2	ENST00000281030.2	NP_003242.1
NDUFC2-KCTD14	NM_001203260.2	c.310+8911T>A		intron_variant			NP_001190189.1
NDUFC2-KCTD14	NM_001203261.2	c.310+8911T>A		intron_variant			NP_001190190.1
NDUFC2-KCTD14	NM_001203262.2	c.166+15492T>A		intron_variant			NP_001190191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THRSP	ENST00000281030.2	c.206A>T	p.Asp69Val	missense_variant	1/2	1	NM_003251.4	ENSP00000281030.2
NDUFC2-KCTD14	ENST00000612612.5	c.310+8911T>A		intron_variant		2		ENSP00000478766.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Oct 06, 2024

The c.206A>T (p.D69V) alteration is located in exon 1 (coding exon 1) of the THRSP gene. This alteration results from a A to T substitution at nucleotide position 206, causing the aspartic acid (D) at amino acid position 69 to be replaced by a valine (V). 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	0.23
BayesDel_addAF	Benign	-0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.026	D
Polyphen		0.94	P
Vest4		0.33
MutPred		0.72		Gain of ubiquitination at K64 (P = 0.1047);
MVP		0.29
MPC		0.48
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.34
gMVP		0.36

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: chr11-77775133;