Genetic Variant NM_181773.5:c.363G>T (chr22-39101449-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_181773.5(APOBEC3H):c.363G>T(p.Lys121Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 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: 𝑓 0.0 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

APOBEC3H
NM_181773.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.647

Publications

30 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.229404).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181773.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
APOBEC3H	NM_181773.5	MANE Select	c.363G>T	p.Lys121Asn	missense	Exon 3 of 5	NP_861438.3
APOBEC3H	NM_001166003.3		c.363G>T	p.Lys121Asn	missense	Exon 3 of 6	NP_001159475.2
APOBEC3H	NM_001166002.3		c.363G>T	p.Lys121Asn	missense	Exon 3 of 5	NP_001159474.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
APOBEC3H	ENST00000442487.8	TSL:3 MANE Select	c.363G>T	p.Lys121Asn	missense	Exon 3 of 5	ENSP00000411754.3
APOBEC3H	ENST00000348946.8	TSL:1	c.363G>T	p.Lys121Asn	missense	Exon 3 of 5	ENSP00000216123.5
APOBEC3H	ENST00000613996.1	TSL:1	c.363G>T	p.Lys121Asn	missense	Exon 2 of 3	ENSP00000482682.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148514

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000274

AC:

AN:

1461434

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727032

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5542

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111948

Other (OTH)

AF:

0.00

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

148514

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72216

African (AFR)

AF:

0.00

AC:

AN:

40104

American (AMR)

AF:

0.00

AC:

AN:

14802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5026

South Asian (SAS)

AF:

0.00

AC:

AN:

4612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67212

Other (OTH)

AF:

0.00

AC:

AN:

2034

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.23

M_CAP

Benign

0.076

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.94

PhyloP100

0.65

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.3

REVEL

Benign

0.053

Sift

Uncertain

0.024

Sift4G

Benign

0.14

Vest4

0.056

MutPred

0.27

Loss of methylation at K121 (P = 0.0613)

MVP

0.068

MPC

0.40

ClinPred

0.17

GERP RS

1.3

Varity_R

0.14

gMVP

0.25

Mutation Taster

=90/10

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

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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