1-13390441-A-G

Position:

• chr1-13390441-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099851.3(PRAMEF17):​c.388A>G​(p.Ser130Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S130N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRAMEF17 NM_001099851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.08

Genes affected

PRAMEF17 (HGNC:29485): (PRAME family member 17) Predicted to be involved in several processes, including negative regulation of apoptotic process; negative regulation of transcription, DNA-templated; and positive regulation of cell population proliferation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15305158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF17	NM_001099851.3	c.388A>G	p.Ser130Gly	missense_variant	2/3	ENST00000376098.4	NP_001093321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF17	ENST00000376098.4	c.388A>G	p.Ser130Gly	missense_variant	2/3	1	NM_001099851.3	ENSP00000365266.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.388A>G (p.S130G) alteration is located in exon 2 (coding exon 2) of the PRAMEF17 gene. This alteration results from a A to G substitution at nucleotide position 388, causing the serine (S) at amino acid position 130 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.9
DANN	Benign	0.55
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.025
Sift	Benign	0.22	T
Sift4G	Benign	0.40	T
Polyphen		1.0	D
Vest4		0.065
MutPred		0.26		Gain of helix (P = 0.0425);
MVP		0.043
MPC		3.1
ClinPred		0.27	T
GERP RS		-0.82
Varity_R		0.054
gMVP		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1640864108; hg19: chr1-13716901;