Genetic Variant NM_006999.6:c.1007C>T (chr5-6739851-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006999.6(TENT4A):c.1007C>T(p.Thr336Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000411 in 1,461,154 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TENT4A
NM_006999.6 missense, splice_region

Scores

Splicing: ADA: 0.05384

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.99

Publications

0 publications found

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]

TENT4A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006999.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT4A	NM_006999.6	MANE Select	c.1007C>T	p.Thr336Met	missense splice_region	Exon 4 of 13	NP_008930.2	Q5XG87-1
	TENT4A	NM_001171805.3		c.1007C>T	p.Thr336Met	missense splice_region	Exon 4 of 13	NP_001165276.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TENT4A	ENST00000230859.8	TSL:1 MANE Select	c.1007C>T	p.Thr336Met	missense splice_region	Exon 4 of 13	ENSP00000230859.7	Q5XG87-1
TENT4A	ENST00000932304.1		c.1007C>T	p.Thr336Met	missense splice_region	Exon 4 of 13	ENSP00000602363.1
TENT4A	ENST00000932305.1		c.1007C>T	p.Thr336Met	missense splice_region	Exon 4 of 12	ENSP00000602364.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251180

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461154

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111396

Other (OTH)

AF:

0.0000166

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.054

Eigen_PC

Benign

0.0074

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.54

MetaSVM

Benign

-0.99

PhyloP100

7.0

PrimateAI

Pathogenic

0.84

REVEL

Benign

0.22

Sift4G

Uncertain

0.0020

Vest4

0.80

MVP

0.53

MPC

2.2

ClinPred

0.98

GERP RS

4.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.0

gMVP

0.65

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.054

dbscSNV1_RF

Benign

0.30

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over