rs12480887

Positions:

• chr20-45798779-A-G

Variant summary

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

The NM_052951.3(DNTTIP1):​c.373-2295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,250 control chromosomes in the GnomAD database, including 1,002 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 0.11 (1002 hom., cov: 32)
• Consequence: DNTTIP1 NM_052951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594

Genes affected

DNTTIP1 (HGNC:16160): (deoxynucleotidyltransferase terminal interacting protein 1) DNTTIP1 binds DNA and enhances the activity of terminal deoxynucleotidyltransferase (TDT, or DNTT; MIM 187410), a DNA polymerase that catalyzes the polymerization of DNA in the absence of a DNA template (Yamashita et al., 2001 [PubMed 11473582]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNTTIP1	NM_052951.3	c.373-2295A>G		intron_variant		ENST00000372622.8	NP_443183.1
DNTTIP1	XM_024451823.2	c.253-2295A>G		intron_variant			XP_024307591.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNTTIP1	ENST00000372622.8	c.373-2295A>G		intron_variant		1	NM_052951.3	ENSP00000361705.3
DNTTIP1	ENST00000456939.5	c.223-2295A>G		intron_variant		5		ENSP00000401024.1
DNTTIP1	ENST00000435014.1	c.151-2295A>G		intron_variant		5		ENSP00000400573.1
DNTTIP1	ENST00000415790.5	c.253-2295A>G		intron_variant		3		ENSP00000392509.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16543 AN: 152132 Hom.: 1006 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0389

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16545 AN: 152250 Hom.: 1002 Cov.: 32 AF XY: 0.111 AC XY: 8279 AN XY: 74442

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.0947

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0390

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.113

Alfa AF: 0.121 Hom.: 1570

Bravo AF: 0.103

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.74

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: rs12480887; hg19: chr20-44427418;