5-6739764-A-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000230859.8(TENT4A):ā€‹c.920A>Cā€‹(p.Glu307Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.000092 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

TENT4A
ENST00000230859.8 missense

Scores

1
5
8

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 6.36
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1551556).
BS2
High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TENT4ANM_006999.6 linkuse as main transcriptc.920A>C p.Glu307Ala missense_variant 4/13 ENST00000230859.8 NP_008930.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TENT4AENST00000230859.8 linkuse as main transcriptc.920A>C p.Glu307Ala missense_variant 4/131 NM_006999.6 ENSP00000230859 Q5XG87-1
TENT4AENST00000631941.2 linkuse as main transcriptc.170A>C p.Glu57Ala missense_variant 4/135 ENSP00000488642 P1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152110
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251438
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461860
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152110
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.000338
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000155
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 09, 2023The c.170A>C (p.E57A) alteration is located in exon 4 (coding exon 3) of the PAPD7 gene. This alteration results from a A to C substitution at nucleotide position 170, causing the glutamic acid (E) at amino acid position 57 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
25
DANN
Uncertain
0.99
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-0.92
T
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.81
D
REVEL
Benign
0.23
Sift4G
Uncertain
0.021
D;T
Vest4
0.65
MVP
0.48
MPC
1.8
ClinPred
0.31
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143476341; hg19: chr5-6739877; API