16-67391048-C-A

Variant names:

• chr16-67391048-C-A
• rs754672026
• NM_015964.4:c.64G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015964.4(TPPP3):​c.64G>T​(p.Asp22Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D22N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TPPP3 NM_015964.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

TPPP3 (HGNC:24162): (tubulin polymerization promoting protein family member 3) Enables tubulin binding activity. Involved in decidualization and microtubule bundle formation. Colocalizes with microtubule bundle and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RNU1-123P (HGNC:48465): (RNA, U1 small nuclear 123, pseudogene)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015964.4. 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
	TPPP3	NM_015964.4	MANE Select	c.64G>T	p.Asp22Tyr	missense	Exon 2 of 4	NP_057048.2	Q9BW30
	TPPP3	NM_016140.4		c.64G>T	p.Asp22Tyr	missense	Exon 3 of 5	NP_057224.2	Q9BW30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPPP3	ENST00000393957.7	TSL:1 MANE Select	c.64G>T	p.Asp22Tyr	missense	Exon 2 of 4	ENSP00000377529.2	Q9BW30
	TPPP3	ENST00000564104.5	TSL:1	c.64G>T	p.Asp22Tyr	missense	Exon 1 of 3	ENSP00000462435.1	Q9BW30
	TPPP3	ENST00000290942.9	TSL:2	c.64G>T	p.Asp22Tyr	missense	Exon 3 of 5	ENSP00000290942.5	Q9BW30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		7.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.55		Loss of disorder (P = 0.0087)
MVP		0.84
MPC		1.3
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.75
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs754672026; hg19: chr16-67424951;