chr21-44873570-C-T

Variant names:

• chr21-44873570-C-T
• NM_004339.4:c.47G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004339.4(PTTG1IP):​c.47G>A​(p.Arg16His) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTTG1IP NM_004339.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.540
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05441025).

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.47G>A	p.Arg16His	missense	Exon 1 of 6	NP_004330.1	P53801
	PTTG1IP	NM_001286822.2		c.47G>A	p.Arg16His	missense	Exon 1 of 3	NP_001273751.1	B4DPZ0
	PTTG1IP	NR_104597.2		n.121G>A		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTTG1IP	ENST00000330938.8	TSL:1 MANE Select	c.47G>A	p.Arg16His	missense	Exon 1 of 6	ENSP00000328325.3	P53801
	PTTG1IP	ENST00000898882.1		c.47G>A	p.Arg16His	missense	Exon 1 of 7	ENSP00000568941.1
	PTTG1IP	ENST00000898881.1		c.47G>A	p.Arg16His	missense	Exon 1 of 6	ENSP00000568940.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1318822 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 650244

African (AFR) AF: 0.00 AC: 0 AN: 26712

American (AMR) AF: 0.00 AC: 0 AN: 26268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23338

East Asian (EAS) AF: 0.00 AC: 0 AN: 28104

South Asian (SAS) AF: 0.00 AC: 0 AN: 72898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5364

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1048666

Other (OTH) AF: 0.00 AC: 0 AN: 54764

GnomAD4 genome Cov.: 34

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	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.54
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.038
Sift	Benign	0.47	T
Sift4G	Benign	0.59	T
Polyphen		0.011	B
Vest4		0.065
MutPred		0.40		Loss of methylation at R16 (P = 0.0083)
MVP		0.14
MPC		0.35
ClinPred		0.16	T
GERP RS		-0.52
PromoterAI		-0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.031
gMVP		0.35
Mutation Taster		=99/1	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

hg19: chr21-46293485;