rs766521799

Variant names:

• chr19-8498418-C-T
• rs766521799
• NM_032152.5:c.1390G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-8498418-C-T
• chr19-8498418-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032152.5(PRAM1):​c.1390G>A​(p.Val464Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000399 in 1,577,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: PRAM1 NM_032152.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.507
• Publications: 0 publications found

Genes affected

PRAM1 (HGNC:30091): (PML-RARA regulated adaptor molecule 1) The protein encoded by this gene is similar to FYN binding protein (FYB/SLAP-130), an adaptor protein involved in T cell receptor mediated signaling. This gene is expressed and regulated during normal myelopoiesis. The expression of this gene is induced by retinoic acid and is inhibited by the expression of PML-RARalpha, a fusion protein of promyelocytic leukemia (PML) and the retinoic acid receptor-alpha (RARalpha). [provided by RefSeq, Jul 2008]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029205114).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032152.5. 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
	PRAM1	NM_032152.5	MANE Select	c.1390G>A	p.Val464Met	missense	Exon 2 of 10	NP_115528.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAM1	ENST00000423345.5	TSL:1 MANE Select	c.1390G>A	p.Val464Met	missense	Exon 2 of 10	ENSP00000408342.2	Q96QH2
	PRAM1	ENST00000880309.1		c.1390G>A	p.Val464Met	missense	Exon 2 of 10	ENSP00000550368.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152238 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000349 AC: 7 AN: 200498 AF XY: 0.0000455

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000455

Gnomad OTH exome AF: 0.000598

GnomAD4 exome AF: 0.0000358 AC: 51 AN: 1424948 Hom.: 0 Cov.: 32 AF XY: 0.0000326 AC XY: 23 AN XY: 704686

African (AFR) AF: 0.0000306 AC: 1 AN: 32702

American (AMR) AF: 0.00 AC: 0 AN: 40782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24176

East Asian (EAS) AF: 0.00 AC: 0 AN: 38762

South Asian (SAS) AF: 0.00 AC: 0 AN: 81704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50642

Middle Eastern (MID) AF: 0.000179 AC: 1 AN: 5586

European-Non Finnish (NFE) AF: 0.0000403 AC: 44 AN: 1091928

Other (OTH) AF: 0.0000852 AC: 5 AN: 58666

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152238 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000252 AC: 3

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	Benign	0.093
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.55
DANN	Benign	0.79
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.51
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.014
Sift	Benign	0.21	T
Sift4G	Benign	0.13	T
Vest4		0.063
MVP		0.055
MPC		0.13
ClinPred		0.088	T
GERP RS		-7.1
Varity_R		0.044
gMVP		0.098
Mutation Taster		=100/0	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: rs766521799; hg19: chr19-8563302; COSMIC: COSV106081523; COSMIC: COSV106081523;