chr22-39100384-C-T

Variant names:

• chr22-39100384-C-T
• rs2146317790
• NM_181773.5:c.106C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181773.5(APOBEC3H):​c.106C>T​(p.Pro36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: APOBEC3H NM_181773.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.50
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091810465).

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.106C>T	p.Pro36Ser	missense	Exon 2 of 5	NP_861438.3	B7TQM3
	APOBEC3H	NM_001166003.3		c.106C>T	p.Pro36Ser	missense	Exon 2 of 6	NP_001159475.2	Q6NTF7-1
	APOBEC3H	NM_001166002.3		c.106C>T	p.Pro36Ser	missense	Exon 2 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.106C>T	p.Pro36Ser	missense	Exon 2 of 5	ENSP00000411754.3	Q6NTF7-3
	APOBEC3H	ENST00000348946.8	TSL:1	c.106C>T	p.Pro36Ser	missense	Exon 2 of 5	ENSP00000216123.5	Q6NTF7-2
	APOBEC3H	ENST00000613996.1	TSL:1	c.106C>T	p.Pro36Ser	missense	Exon 1 of 3	ENSP00000482682.1	A0A087WZI3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461826 Hom.: 0 Cov.: 42 AF XY: 0.00000275 AC XY: 2 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

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	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.24
DANN	Benign	0.65
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.5
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.084
Sift	Benign	0.66	T
Sift4G	Benign	0.47	T
Vest4		0.13
MutPred		0.47		Gain of sheet (P = 0.0827)
MVP		0.26
MPC		0.40
ClinPred		0.12	T
GERP RS		0.29
PromoterAI		0.29	Neutral
Varity_R		0.23
gMVP		0.22
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs2146317790; hg19: chr22-39496389;