21-44850461-G-C

Variant names:

• chr21-44850461-G-C
• rs84193
• NM_004339.4:c.*1120C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004339.4(PTTG1IP):​c.*1120C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,172 control chromosomes in the GnomAD database, including 28,486 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28468 hom., cov: 33)
  • Exomes 𝑓: 0.74 (18 hom.)
• Consequence: PTTG1IP NM_004339.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTTG1IP	NM_004339.4	MANE Select	c.*1120C>G		3_prime_UTR	Exon 6 of 6	NP_004330.1
	PTTG1IP	NM_001286822.2		c.*906C>G		3_prime_UTR	Exon 3 of 3	NP_001273751.1
	PTTG1IP	NR_104597.2		n.1628C>G		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTTG1IP	ENST00000330938.8	TSL:1 MANE Select	c.*1120C>G		3_prime_UTR	Exon 6 of 6	ENSP00000328325.3
	PTTG1IP	ENST00000898882.1		c.*1120C>G		3_prime_UTR	Exon 7 of 7	ENSP00000568941.1
	PTTG1IP	ENST00000898881.1		c.*1120C>G		3_prime_UTR	Exon 6 of 6	ENSP00000568940.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92413 AN: 151988 Hom.: 28442 Cov.: 33

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.742 AC: 49 AN: 66 Hom.: 18 Cov.: 0 AF XY: 0.771 AC XY: 37 AN XY: 48

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.720 AC: 36 AN: 50

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.608 AC: 92495 AN: 152106 Hom.: 28468 Cov.: 33 AF XY: 0.610 AC XY: 45383 AN XY: 74362

African (AFR) AF: 0.534 AC: 22153 AN: 41494

American (AMR) AF: 0.600 AC: 9181 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2203 AN: 3472

East Asian (EAS) AF: 0.801 AC: 4143 AN: 5170

South Asian (SAS) AF: 0.706 AC: 3403 AN: 4822

European-Finnish (FIN) AF: 0.628 AC: 6645 AN: 10580

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42757 AN: 67968

Other (OTH) AF: 0.633 AC: 1334 AN: 2108

Alfa AF: 0.499 Hom.: 1477

Bravo AF: 0.602

Asia WGS AF: 0.745 AC: 2591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.51
PhyloP100		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs84193; hg19: chr21-46270376;