20-44489404-G-A

Position:

• chr20-44489404-G-A

Variant summary

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

The NM_001039199.3(TTPAL):​c.892G>A​(p.Val298Met) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTPAL NM_001039199.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

Genes affected

TTPAL (HGNC:16114): (alpha tocopherol transfer protein like) Predicted to enable phosphatidylinositol bisphosphate binding activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TTPAL (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=0.1856108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTPAL	NM_001039199.3	c.892G>A	p.Val298Met	missense_variant	5/5	ENST00000262605.9	NP_001034288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTPAL	ENST00000262605.9	c.892G>A	p.Val298Met	missense_variant	5/5	1	NM_001039199.3	ENSP00000262605.4

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

Mar 15, 2024

The c.892G>A (p.V298M) alteration is located in exon 6 (coding exon 4) of the TTPAL gene. This alteration results from a G to A substitution at nucleotide position 892, causing the valine (V) at amino acid position 298 to be replaced by a methionine (M). 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	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.4	L;L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.51	N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.061	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.44	B;B;.
Vest4		0.071
MutPred		0.42		Loss of methylation at K299 (P = 0.0158);Loss of methylation at K299 (P = 0.0158);.;
MVP		0.12
MPC		0.40
ClinPred		0.46	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.55

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: chr20-43118045;