20-45795358-C-G

Position:

• chr20-45795358-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052951.3(DNTTIP1):​c.287C>G​(p.Ala96Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A96T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNTTIP1 NM_052951.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.41

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNTTIP1	NM_052951.3	c.287C>G	p.Ala96Gly	missense_variant	4/13	ENST00000372622.8
DNTTIP1	XM_024451823.2	c.167C>G	p.Ala56Gly	missense_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNTTIP1	ENST00000372622.8	c.287C>G	p.Ala96Gly	missense_variant	4/13	1	NM_052951.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2022

The c.287C>G (p.A96G) alteration is located in exon 4 (coding exon 4) of the DNTTIP1 gene. This alteration results from a C to G substitution at nucleotide position 287, causing the alanine (A) at amino acid position 96 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	2.0	M;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.29
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.17	T;D;D
Polyphen		0.99	D;.;.
Vest4		0.87
MutPred		0.47		Loss of helix (P = 0.0068);.;.;
MVP		0.69
MPC		0.98
ClinPred		0.82	D
GERP RS		5.5
Varity_R		0.60
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-44423997;