NM_001039199.3:c.892G>A

Variant names:

• chr20-44489404-G-A
• NM_001039199.3:c.892G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1856108).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039199.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTPAL	NM_001039199.3	MANE Select	c.892G>A	p.Val298Met	missense	Exon 5 of 5	NP_001034288.1	Q9BTX7
	TTPAL	NM_024331.5		c.892G>A	p.Val298Met	missense	Exon 6 of 6	NP_077307.2	Q9BTX7
	TTPAL	NM_001261839.2		c.790G>A	p.Val264Met	missense	Exon 5 of 5	NP_001248768.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTPAL	ENST00000262605.9	TSL:1 MANE Select	c.892G>A	p.Val298Met	missense	Exon 5 of 5	ENSP00000262605.4	Q9BTX7
	TTPAL	ENST00000372904.7	TSL:1	c.892G>A	p.Val298Met	missense	Exon 6 of 6	ENSP00000361995.3	Q9BTX7
	TTPAL	ENST00000901707.1		c.892G>A	p.Val298Met	missense	Exon 5 of 5	ENSP00000571766.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.9
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.51	N
REVEL	Uncertain	0.32
Sift	Benign	0.061	T
Sift4G	Benign	0.21	T
Polyphen		0.44	B
Vest4		0.071
MutPred		0.42		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
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

hg19: chr20-43118045;