rs372574211

Variant names:

• chr19-8490693-C-A
• rs372574211
• NM_032152.5:c.1807G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-8490693-C-A
• chr19-8490693-C-G
• chr19-8490693-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032152.5(PRAM1):​c.1807G>T​(p.Gly603Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G603R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAM1 NM_032152.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.86

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAM1	NM_032152.5	c.1807G>T	p.Gly603Trp	missense_variant	Exon 7 of 10	ENST00000423345.5	NP_115528.4
PRAM1	XM_011528352.3	c.1813G>T	p.Gly605Trp	missense_variant	Exon 7 of 9		XP_011526654.1
PRAM1	XM_005272502.3	c.1807G>T	p.Gly603Trp	missense_variant	Exon 7 of 9		XP_005272559.1
PRAM1	XM_011528353.3	c.1813G>T	p.Gly605Trp	missense_variant	Exon 7 of 10		XP_011526655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRAM1	ENST00000423345.5	c.1807G>T	p.Gly603Trp	missense_variant	Exon 7 of 10	1	NM_032152.5	ENSP00000408342.2
PRAM1	ENST00000594696.1	n.1097G>T		non_coding_transcript_exon_variant	Exon 3 of 6	5
PRAM1	ENST00000599698.5	n.183G>T		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455140 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723378

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Uncertain	0.99
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.20
Sift	Benign	0.090	T
Sift4G	Uncertain	0.0020	D
Vest4		0.63
MVP		0.53
MPC		0.63
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.16
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs372574211; hg19: chr19-8555577;