20-44484517-T-C

Variant names:

• chr20-44484517-T-C
• NM_001039199.3:c.626T>C

Variant summary

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

The NM_001039199.3(TTPAL):​c.626T>C​(p.Ile209Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTPAL NM_001039199.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25

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

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 rank	MANE	Protein	UniProt
TTPAL	NM_001039199.3	c.626T>C	p.Ile209Thr	missense_variant	Exon 3 of 5	ENST00000262605.9	NP_001034288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTPAL	ENST00000262605.9	c.626T>C	p.Ile209Thr	missense_variant	Exon 3 of 5	1	NM_001039199.3	ENSP00000262605.4
TTPAL	ENST00000372904.7	c.626T>C	p.Ile209Thr	missense_variant	Exon 4 of 6	1		ENSP00000361995.3
TTPAL	ENST00000456317.1	c.537+89T>C		intron_variant	Intron 3 of 4	2		ENSP00000412720.1
TTPAL	ENST00000372906.2	c.445+4073T>C		intron_variant	Intron 2 of 2	3		ENSP00000361997.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1424392 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 702872

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.626T>C (p.I209T) alteration is located in exon 4 (coding exon 2) of the TTPAL gene. This alteration results from a T to C substitution at nucleotide position 626, causing the isoleucine (I) at amino acid position 209 to be replaced by a threonine (T). 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	0.30
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.36	N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.27	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.18	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.31	B;B
Vest4		0.73
MutPred		0.70		Loss of stability (P = 0.0375);Loss of stability (P = 0.0375);
MVP		0.12
MPC		0.56
ClinPred		0.68	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.81

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: chr20-43113157; COSMIC: COSV52829755; COSMIC: COSV52829755;