1-13262644-C-G

Position:

• chr1-13262644-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001013407.5(PRAMEF5):​c.964C>G​(p.Gln322Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 2)
• Consequence: PRAMEF5 NM_001013407.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.170

Genes affected

PRAMEF5 (HGNC:27995): (PRAME family member 5) 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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12069121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAMEF5	NM_001013407.5	c.964C>G	p.Gln322Glu	missense_variant	4/4	ENST00000622421.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAMEF5	ENST00000622421.3	c.964C>G	p.Gln322Glu	missense_variant	4/4	1	NM_001013407.5	P1

Frequencies

GnomAD3 genomes Cov.: 2

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 2

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

Aug 09, 2021

The c.964C>G (p.Q322E) alteration is located in exon 4 (coding exon 3) of the PRAMEF5 gene. This alteration results from a C to G substitution at nucleotide position 964, causing the glutamine (Q) at amino acid position 322 to be replaced by a glutamic acid (E). 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	0.084
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.034	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.64	T
Sift4G	Uncertain	0.045	D
Vest4		0.062
MVP		0.014
ClinPred		0.12	T
GERP RS		1.3
Varity_R		0.034
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-13368266;