rs780778324

Variant names:

• chr5-893075-A-C
• NM_004237.4:c.77A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-893075-A-C
• chr5-893075-A-G
• chr5-893075-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_004237.4(TRIP13):​c.77A>C​(p.His26Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. H26R) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIP13 NM_004237.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

Genes affected

TRIP13 (HGNC:12307): (thyroid hormone receptor interactor 13) This gene encodes a protein that interacts with thyroid hormone receptors, also known as hormone-dependent transcription factors. The gene product interacts specifically with the ligand binding domain. This gene is one of several that may play a role in early-stage non-small cell lung cancer. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr5-893075-A-G is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.24072132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP13	NM_004237.4	c.77A>C	p.His26Pro	missense_variant	Exon 1 of 13	ENST00000166345.8	NP_004228.1
TRIP13	NM_001166260.2	c.77A>C	p.His26Pro	missense_variant	Exon 1 of 9		NP_001159732.1
TRIP13	XM_011514163.2	c.77A>C	p.His26Pro	missense_variant	Exon 1 of 14		XP_011512465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP13	ENST00000166345.8	c.77A>C	p.His26Pro	missense_variant	Exon 1 of 13	1	NM_004237.4	ENSP00000166345.3
TRIP13	ENST00000512024.5	n.192A>C		non_coding_transcript_exon_variant	Exon 1 of 9	1
TRIP13	ENST00000508456.1	n.51A>C		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444434 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 717804

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: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	14
DANN	Benign	0.61
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.81	L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.34
Sift	Benign	0.20	T
Sift4G	Benign	0.20	T
Polyphen		0.031	B
Vest4		0.31
MutPred		0.33		Gain of loop (P = 0.0312);
MVP		0.67
MPC		0.95
ClinPred		0.11	T
GERP RS		-4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.83

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: chr5-893190;