5-6742580-A-G

Position:

• chr5-6742580-A-G

Variant summary

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

The ENST00000230859.8(TENT4A):​c.1099A>G​(p.Ile367Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TENT4A ENST00000230859.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.40

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT4A	NM_006999.6	c.1099A>G	p.Ile367Val	missense_variant	5/13	ENST00000230859.8	NP_008930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENT4A	ENST00000230859.8	c.1099A>G	p.Ile367Val	missense_variant	5/13	1	NM_006999.6	ENSP00000230859
TENT4A	ENST00000631941.2	c.349A>G	p.Ile117Val	missense_variant	5/13	5		ENSP00000488642	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

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

Mar 18, 2024

The c.349A>G (p.I117V) alteration is located in exon 5 (coding exon 4) of the PAPD7 gene. This alteration results from a A to G substitution at nucleotide position 349, causing the isoleucine (I) at amino acid position 117 to be replaced by a valine (V). 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	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0076	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.69	T
REVEL	Benign	0.20
Sift4G	Pathogenic	0.0	D;T
Vest4		0.66
MVP		0.44
MPC		1.0
ClinPred		0.94	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.65

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: chr5-6742693;