Variant 22-39101279-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181773.5(APOBEC3H):c.193T>A(p.Ser65Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

APOBEC3H
NM_181773.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.167

Variant links:

Genes affected

APOBEC3H (HGNC:24100): (apolipoprotein B mRNA editing enzyme catalytic subunit 3H) This gene encodes a member of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 family of proteins. The encoded protein is a cytidine deaminase that has antiretroviral activity by generating lethal hypermutations in viral genomes. Polymorphisms and alternative splicing in this gene influence its antiretroviral activity and are associated with increased resistence to human immunodeficiency virus type 1 infection in certain populations. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

APOBEC3H links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17900696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3H	NM_181773.5 linkuse as main transcript	c.193T>A	p.Ser65Thr	missense_variant	3/5	ENST00000442487.8	NP_861438.3	Q6NTF7-3B7TQM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8 linkuse as main transcript	c.193T>A	p.Ser65Thr	missense_variant	3/5	3	NM_181773.5	ENSP00000411754.3		Q6NTF7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.193T>A (p.S65T) alteration is located in exon 3 (coding exon 2) of the APOBEC3H gene. This alteration results from a T to A substitution at nucleotide position 193, causing the serine (S) at amino acid position 65 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

.;T;.;T;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.66

T;T;T;.;T;.

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.5

.;M;M;M;M;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

N;.;N;N;N;.

REVEL

Benign

0.23

Sift

Benign

0.035

D;.;T;D;T;.

Sift4G

Uncertain

0.017

D;D;D;D;D;D

Vest4

0.17

MutPred

0.55

Gain of glycosylation at S65 (P = 0.1609);Gain of glycosylation at S65 (P = 0.1609);Gain of glycosylation at S65 (P = 0.1609);Gain of glycosylation at S65 (P = 0.1609);Gain of glycosylation at S65 (P = 0.1609);Gain of glycosylation at S65 (P = 0.1609);

MVP

0.043

MPC

0.69

ClinPred

0.41

GERP RS

1.1

Varity_R

0.20

gMVP

0.099

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over