chr20-45801433-A-C

Position:

• chr20-45801433-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052951.3(DNTTIP1):​c.473A>C​(p.His158Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 1.43

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19308236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNTTIP1	NM_052951.3	c.473A>C	p.His158Pro	missense_variant	6/13	ENST00000372622.8
DNTTIP1	XM_024451823.2	c.353A>C	p.His118Pro	missense_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNTTIP1	ENST00000372622.8	c.473A>C	p.His158Pro	missense_variant	6/13	1	NM_052951.3	P1
DNTTIP1	ENST00000456939.5	c.326A>C	p.His109Pro	missense_variant	5/12	5
DNTTIP1	ENST00000435014.1	c.254A>C	p.His85Pro	missense_variant	4/10	5
DNTTIP1	ENST00000415790.5	c.353A>C	p.His118Pro	missense_variant	5/6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Nov 07, 2023

The c.473A>C (p.H158P) alteration is located in exon 6 (coding exon 6) of the DNTTIP1 gene. This alteration results from a A to C substitution at nucleotide position 473, causing the histidine (H) at amino acid position 158 to be replaced by a proline (P). 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	0.063
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	0.016
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	0.84	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.070
Sift	Benign	0.21	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.96	D;.
Vest4		0.32
MutPred		0.28		Loss of helix (P = 0.0237);.;
MVP		0.50
MPC		1.5
ClinPred		0.48	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-44430072;