5-6738710-G-T

Position:

• chr5-6738710-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000230859.8(TENT4A):​c.868G>T​(p.Gly290Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TENT4A ENST00000230859.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.93

Genes affected

TENT4A (HGNC:16705): (terminal nucleotidyltransferase 4A) The protein encoded by this gene is a DNA polymerase that is likely involved in DNA repair. In addition, the encoded protein may be required for sister chromatid adhesion. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT4A	NM_006999.6	c.868G>T	p.Gly290Cys	missense_variant	3/13	ENST00000230859.8	NP_008930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENT4A	ENST00000230859.8	c.868G>T	p.Gly290Cys	missense_variant	3/13	1	NM_006999.6	ENSP00000230859
TENT4A	ENST00000631941.2	c.118G>T	p.Gly40Cys	missense_variant	3/13	5		ENSP00000488642	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 05, 2023

The c.118G>T (p.G40C) alteration is located in exon 3 (coding exon 2) of the PAPD7 gene. This alteration results from a G to T substitution at nucleotide position 118, causing the glycine (G) at amino acid position 40 to be replaced by a cysteine (C). 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
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	33
DANN	Uncertain	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Pathogenic	1.0	D
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.91	D
REVEL	Pathogenic	0.73
Sift4G	Pathogenic	0.0	D;D
Vest4		0.96
MutPred		0.27		.;Loss of methylation at R39 (P = 0.049);
MVP		0.98
MPC		2.3
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.99

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: chr5-6738823; COSMIC: COSV105074062; COSMIC: COSV105074062;