22-39101471-T-A

Variant names:

• chr22-39101471-T-A
• rs754592108
• NM_181773.5:c.385T>A

Variant summary

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

The NM_181773.5(APOBEC3H):​c.385T>A​(p.Ser129Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,450,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: APOBEC3H NM_181773.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.138
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.2241073).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3H	NM_181773.5	MANE Select	c.385T>A	p.Ser129Thr	missense	Exon 3 of 5	NP_861438.3	B7TQM3
	APOBEC3H	NM_001166003.3		c.385T>A	p.Ser129Thr	missense	Exon 3 of 6	NP_001159475.2	Q6NTF7-1
	APOBEC3H	NM_001166002.3		c.385T>A	p.Ser129Thr	missense	Exon 3 of 5	NP_001159474.2	B7TQM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3H	ENST00000442487.8	TSL:3 MANE Select	c.385T>A	p.Ser129Thr	missense	Exon 3 of 5	ENSP00000411754.3	Q6NTF7-3
	APOBEC3H	ENST00000348946.8	TSL:1	c.385T>A	p.Ser129Thr	missense	Exon 3 of 5	ENSP00000216123.5	Q6NTF7-2
	APOBEC3H	ENST00000613996.1	TSL:1	c.385T>A	p.Ser129Thr	missense	Exon 2 of 3	ENSP00000482682.1	A0A087WZI3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249842 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.00000620 AC: 9 AN: 1450808 Hom.: 0 Cov.: 42 AF XY: 0.0000111 AC XY: 8 AN XY: 721662

African (AFR) AF: 0.00 AC: 0 AN: 33226

American (AMR) AF: 0.00 AC: 0 AN: 44320

Ashkenazi Jewish (ASJ) AF: 0.0000389 AC: 1 AN: 25732

East Asian (EAS) AF: 0.00 AC: 0 AN: 38812

South Asian (SAS) AF: 0.00 AC: 0 AN: 86124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52504

Middle Eastern (MID) AF: 0.000587 AC: 3 AN: 5114

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105336

Other (OTH) AF: 0.0000838 AC: 5 AN: 59640

GnomAD4 genome Cov.: 21

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.14
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.045	D
Vest4		0.088
MutPred		0.66		Loss of loop (P = 0.1242)
MVP		0.068
MPC		0.50
ClinPred		0.18	T
GERP RS		-0.32
Varity_R		0.16
gMVP		0.25
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs754592108; hg19: chr22-39497476;