7-102396433-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024653.4(PRKRIP1):c.22T>G(p.Ser8Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRKRIP1 NM_024653.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780

Genes affected

PRKRIP1 (HGNC:21894): (PRKR interacting protein 1) Predicted to enable double-stranded RNA binding activity; protein kinase binding activity; and protein kinase inhibitor activity. Involved in renal system process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LOC100630923 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045025826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKRIP1	NM_024653.4	c.22T>G	p.Ser8Ala	missense_variant	1/6	ENST00000397912.3
LOC100630923	NR_038967.1	n.912-1187T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKRIP1	ENST00000397912.3	c.22T>G	p.Ser8Ala	missense_variant	1/6	1	NM_024653.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Dec 06, 2022

The c.22T>G (p.S8A) alteration is located in exon 1 (coding exon 1) of the PRKRIP1 gene. This alteration results from a T to G substitution at nucleotide position 22, causing the serine (S) at amino acid position 8 to be replaced by an alanine (A). 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	0.052
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	9.4
Dann	Benign	0.93
DEOGEN2	Benign	0.0038	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.017	N
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	0.62	D;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.046
Sift	Benign	0.13	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0	B;B
Vest4		0.088
MutPred		0.10		Loss of phosphorylation at S8 (P = 0.0018);Loss of phosphorylation at S8 (P = 0.0018);
MVP		0.13
MPC		0.21
ClinPred		0.049	T
GERP RS		-0.46
Varity_R		0.057
gMVP		0.27

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: rs1554570330; hg19: chr7-102036880;