rs84193

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr21-44850461-G-C
• chr21-44850461-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTTG1IP	NM_004339.4	c.*1120C>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000330938.8	NP_004330.1
PTTG1IP	NM_001286822.2	c.*906C>G		3_prime_UTR_variant	Exon 3 of 3		NP_001273751.1
PTTG1IP	NR_104597.2	n.1628C>G		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTTG1IP	ENST00000330938	c.*1120C>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_004339.4	ENSP00000328325.3
PTTG1IP	ENST00000445724	c.*906C>G		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000395374.2
PTTG1IP	ENST00000397887	c.*1120C>G		3_prime_UTR_variant	Exon 4 of 4	4		ENSP00000380984.3

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

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.720

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.633

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs84193; hg19: chr21-46270376;