14-55436786-T-G

Position:

• chr14-55436786-T-G

Variant summary

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

The NM_199047.3(TBPL2):​c.287A>C​(p.Gln96Pro) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBPL2 NM_199047.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.201

Genes affected

TBPL2 (HGNC:19841): (TATA-box binding protein like 2) Predicted to enable RNA polymerase II general transcription initiation factor activity. Predicted to be involved in DNA-templated transcription, initiation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FBXO34 (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=0.07698512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBPL2	NM_199047.3	c.287A>C	p.Gln96Pro	missense_variant	2/7	ENST00000247219.6
FBXO34	XR_007064022.1	n.2983-130T>G		intron_variant, non_coding_transcript_variant
FBXO34	XR_007064023.1	n.2941-6041T>G		intron_variant, non_coding_transcript_variant
FBXO34	XR_007064024.1	n.2983-1156T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBPL2	ENST00000247219.6	c.287A>C	p.Gln96Pro	missense_variant	2/7	1	NM_199047.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Nov 12, 2021

The c.383A>C (p.Q128P) alteration is located in exon 2 (coding exon 2) of the TBPL2 gene. This alteration results from a A to C substitution at nucleotide position 383, causing the glutamine (Q) at amino acid position 128 to be replaced by a proline (P). 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	0.068
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	10
DANN	Benign	0.92
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.024
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.064	T
Polyphen		0.0030	B
Vest4		0.35
MutPred		0.21		Gain of relative solvent accessibility (P = 0.005);
MVP		0.19
MPC		0.13
ClinPred		0.34	T
GERP RS		-0.70
Varity_R		0.28
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr14-55903504;