NM_001039199.3:c.157T>C

Variant names:

• chr20-44480156-T-C
• NM_001039199.3:c.157T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001039199.3(TTPAL):​c.157T>C​(p.Trp53Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TTPAL NM_001039199.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2652644).

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.157T>C	p.Trp53Arg	missense	Exon 2 of 5	NP_001034288.1	Q9BTX7
	TTPAL	NM_024331.5		c.157T>C	p.Trp53Arg	missense	Exon 3 of 6	NP_077307.2	Q9BTX7
	TTPAL	NM_001261839.2		c.157T>C	p.Trp53Arg	missense	Exon 2 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.157T>C	p.Trp53Arg	missense	Exon 2 of 5	ENSP00000262605.4	Q9BTX7
	TTPAL	ENST00000372904.7	TSL:1	c.157T>C	p.Trp53Arg	missense	Exon 3 of 6	ENSP00000361995.3	Q9BTX7
	TTPAL	ENST00000901707.1		c.157T>C	p.Trp53Arg	missense	Exon 2 of 5	ENSP00000571766.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	0.97
DEOGEN2	Benign	0.019	T
Eigen	Benign	0.069
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	-2.5	N
PhyloP100		4.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.55
Sift	Benign	0.15	T
Sift4G	Benign	0.39	T
Polyphen		0.95	P
Vest4		0.77
MutPred		0.36		Gain of disorder (P = 5e-04)
MVP		0.082
MPC		1.6
ClinPred		0.77	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.33
gMVP		0.79
Mutation Taster		=45/55	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr20-43108796;