NM_016045.3:c.470G>A

Variant names:

• chr20-59035122-C-T
• rs774977555
• NM_016045.3:c.470G>A

Variant summary

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

The NM_016045.3(PRELID3B):​c.470G>A​(p.Arg157Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,606,294 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: PRELID3B NM_016045.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

PRELID3B (HGNC:15892): (PRELI domain containing 3B) Predicted to enable phosphatidic acid transfer activity. Predicted to be involved in phospholipid transport. Predicted to be active in mitochondrial intermembrane space. [provided by Alliance of Genome Resources, Apr 2022]

SLMO2-ATP5E (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016045.3. 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
	PRELID3B	NM_016045.3	MANE Select	c.470G>A	p.Arg157Gln	missense	Exon 6 of 6	NP_057129.2	Q9Y3B1-1
	PRELID3B	NM_001256403.2		c.380G>A	p.Arg127Gln	missense	Exon 5 of 5	NP_001243332.1	Q9Y3B1-2
	SLMO2-ATP5E	NR_037929.1		n.586G>A		non_coding_transcript_exon	Exon 6 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRELID3B	ENST00000355937.9	TSL:1 MANE Select	c.470G>A	p.Arg157Gln	missense	Exon 6 of 6	ENSP00000348206.4	Q9Y3B1-1
	PRELID3B	ENST00000852164.1		c.440G>A	p.Arg147Gln	missense	Exon 6 of 6	ENSP00000522223.1
	PRELID3B	ENST00000371033.9	TSL:2	c.380G>A	p.Arg127Gln	missense	Exon 5 of 5	ENSP00000360072.5	Q9Y3B1-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151978 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000164 AC: 4 AN: 243376 AF XY: 0.0000151

Gnomad AFR exome AF: 0.0000651

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000570

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000220 AC: 32 AN: 1454316 Hom.: 0 Cov.: 32 AF XY: 0.0000221 AC XY: 16 AN XY: 723508

African (AFR) AF: 0.00 AC: 0 AN: 33024

American (AMR) AF: 0.00 AC: 0 AN: 42898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25872

East Asian (EAS) AF: 0.00 AC: 0 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 85056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.0000280 AC: 31 AN: 1108910

Other (OTH) AF: 0.0000167 AC: 1 AN: 60028

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151978 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74216

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41346

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000166 AC: 2

ClinVar

ClinVar submissions

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	Pathogenic	0.75
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.98	T
PhyloP100		7.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.29
Sift	Benign	0.077	T
Sift4G	Benign	0.23	T
Polyphen		0.030	B
Vest4		0.68
MVP		0.39
MPC		0.34
ClinPred		0.84	D
GERP RS		5.7
Varity_R		0.62
gMVP		0.85
Mutation Taster		=20/80	disease causing

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: rs774977555; hg19: chr20-57610177;