rs149230223

Variant names:

• chr21-44856245-C-G
• rs149230223
• NM_004339.4:c.397G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-44856245-C-G
• chr21-44856245-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004339.4(PTTG1IP):​c.397G>C​(p.Glu133Gln) 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. 14/22 in silico tools predict a benign 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. E133K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTTG1IP NM_004339.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 0 publications found

Genes affected

PTTG1IP (HGNC:13524): (PTTG1 interacting protein) This gene encodes a single-pass type I integral membrane protein, which binds to pituitary tumor-transforming 1 protein (PTTG1), and facilitates translocation of PTTG1 into the nucleus. Coexpression of this protein and PTTG1 induces transcriptional activation of basic fibroblast growth factor. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2013]

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=0.22869837).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004339.4. 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
	PTTG1IP	NM_004339.4	MANE Select	c.397G>C	p.Glu133Gln	missense	Exon 4 of 6	NP_004330.1	P53801
	PTTG1IP	NM_001286822.2		c.169-4618G>C		intron	N/A	NP_001273751.1	B4DPZ0
	PTTG1IP	NR_104597.2		n.362G>C		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTTG1IP	ENST00000330938.8	TSL:1 MANE Select	c.397G>C	p.Glu133Gln	missense	Exon 4 of 6	ENSP00000328325.3	P53801
	PTTG1IP	ENST00000898882.1		c.397G>C	p.Glu133Gln	missense	Exon 4 of 7	ENSP00000568941.1
	PTTG1IP	ENST00000898881.1		c.397G>C	p.Glu133Gln	missense	Exon 4 of 6	ENSP00000568940.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Benign	0.073
Eigen_PC	Benign	-0.015
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		1.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.14
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.023	D
Polyphen		0.93	P
Vest4		0.25
MutPred		0.13		Loss of ubiquitination at K135 (P = 0.0736)
MVP		0.68
MPC		0.70
ClinPred		0.90	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.33
Mutation Taster		=88/12	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: rs149230223; hg19: chr21-46276160;