chr20-44484517-T-C

Variant names:

• chr20-44484517-T-C
• rs2122862869
• NM_001039199.3:c.626T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.626T>C	p.Ile209Thr	missense	Exon 3 of 5	NP_001034288.1	Q9BTX7
	TTPAL	NM_024331.5		c.626T>C	p.Ile209Thr	missense	Exon 4 of 6	NP_077307.2	Q9BTX7
	TTPAL	NM_001261839.2		c.537+89T>C		intron	N/A	NP_001248768.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTPAL	ENST00000262605.9	TSL:1 MANE Select	c.626T>C	p.Ile209Thr	missense	Exon 3 of 5	ENSP00000262605.4	Q9BTX7
	TTPAL	ENST00000372904.7	TSL:1	c.626T>C	p.Ile209Thr	missense	Exon 4 of 6	ENSP00000361995.3	Q9BTX7
	TTPAL	ENST00000901707.1		c.626T>C	p.Ile209Thr	missense	Exon 3 of 5	ENSP00000571766.1

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

African (AFR) AF: 0.00 AC: 0 AN: 32948

American (AMR) AF: 0.00 AC: 0 AN: 44296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25366

East Asian (EAS) AF: 0.00 AC: 0 AN: 38900

South Asian (SAS) AF: 0.00 AC: 0 AN: 84206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081968

Other (OTH) AF: 0.00 AC: 0 AN: 58434

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	0.30
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	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
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.36	N
PhyloP100		6.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.27	N
REVEL	Uncertain	0.30
Sift	Benign	0.18	T
Sift4G	Benign	0.12	T
Polyphen		0.31	B
Vest4		0.73
MutPred		0.70		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
Mutation Taster		=58/42	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

dbSNP: rs2122862869; hg19: chr20-43113157; COSMIC: COSV52829755; COSMIC: COSV52829755;