Genetic Variant TENT5D:p.His45Tyr (chrX-80442672-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152630.5(TENT5D):c.133C>T(p.His45Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000678 in 1,209,162 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., 12 hem., cov: 23)

Exomes 𝑓: 0.000043 ( 0 hom. 12 hem. )

Consequence

TENT5D
NM_152630.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

Publications

0 publications found

Variant links:

Genes affected

TENT5D (HGNC:28399): (terminal nucleotidyltransferase 5D) Antibodies against the protein encoded by this gene were found only in plasma from cancer patients. While it may be a target for immunotherapy, the function of this gene is unknown. [provided by RefSeq, Dec 2009]

TENT5D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01854831).

BS2

High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT5D	NM_152630.5 link	c.133C>T	p.His45Tyr	missense_variant	Exon 3 of 3	ENST00000308293.6	NP_689843.1	Q8NEK8
TENT5D	NM_001170574.2 link	c.133C>T	p.His45Tyr	missense_variant	Exon 5 of 5		NP_001164045.1	Q8NEK8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENT5D	ENST00000308293.6 link	c.133C>T	p.His45Tyr	missense_variant	Exon 3 of 3	1	NM_152630.5	ENSP00000308575.5		Q8NEK8
TENT5D	ENST00000538312.5 link	c.133C>T	p.His45Tyr	missense_variant	Exon 5 of 5	2		ENSP00000443410.1		Q8NEK8

Frequencies

GnomAD3 genomes

AF:

0.000313

AC:

AN:

111693

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000384

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:

0.000667

GnomAD2 exomes

AF:

0.0000931

AC:

AN:

182625

AF XY:

0.0000742

show subpopulations

Gnomad AFR exome

AF:

0.000912

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000428

AC:

AN:

1097420

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

363090

show subpopulations

African (AFR)

AF:

0.00148

AC:

AN:

26373

American (AMR)

AF:

0.000142

AC:

AN:

35150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19347

East Asian (EAS)

AF:

0.00

AC:

AN:

30187

South Asian (SAS)

AF:

0.00

AC:

AN:

54114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841560

Other (OTH)

AF:

0.0000434

AC:

AN:

46054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.000313

AC:

AN:

111742

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

AN XY:

34024

show subpopulations

African (AFR)

AF:

0.000972

AC:

AN:

30879

American (AMR)

AF:

0.000383

AC:

AN:

10441

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2641

East Asian (EAS)

AF:

0.00

AC:

AN:

3532

South Asian (SAS)

AF:

0.00

AC:

AN:

2708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53010

Other (OTH)

AF:

0.000659

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 11, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.133C>T (p.H45Y) alteration is located in exon 5 (coding exon 1) of the FAM46D gene. This alteration results from a C to T substitution at nucleotide position 133, causing the histidine (H) at amino acid position 45 to be replaced by a tyrosine (Y). 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

0.073

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.043

T;T

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.69

T;.

M_CAP

Benign

0.0068

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.1

PhyloP100

1.7

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.056

Sift

Uncertain

0.026

D;D

Sift4G

Uncertain

0.026

D;D

Polyphen

0.66

P;P

Vest4

0.27

MVP

0.11

MPC

0.86

ClinPred

0.031

GERP RS

3.5

Varity_R

0.29

gMVP

0.48

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over