21-44872823-T-C

Position:

• chr21-44872823-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004339.4(PTTG1IP):​c.115+679A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,320 control chromosomes in the GnomAD database, including 34,767 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 0.67 (34756 hom., cov: 35)
  • Exomes 𝑓: 0.59 (11 hom.)
• Consequence: PTTG1IP NM_004339.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTTG1IP	NM_004339.4	c.115+679A>G		intron_variant		ENST00000330938.8	NP_004330.1
PTTG1IP	NM_001286822.2	c.115+679A>G		intron_variant			NP_001273751.1
PTTG1IP	NR_104597.2	n.189+679A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTTG1IP	ENST00000330938.8	c.115+679A>G		intron_variant		1	NM_004339.4	ENSP00000328325	P1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 102038 AN: 152132 Hom.: 34692 Cov.: 35

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.683

GnomAD4 exome AF: 0.586 AC: 41 AN: 70 Hom.: 11 Cov.: 0 AF XY: 0.648 AC XY: 35 AN XY: 54

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.671 AC: 102166 AN: 152250 Hom.: 34756 Cov.: 35 AF XY: 0.670 AC XY: 49897 AN XY: 74434

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.687

Alfa AF: 0.485 Hom.: 1192

Bravo AF: 0.678

Asia WGS AF: 0.724 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs235371; hg19: chr21-46292738;