11-32840107-A-G

Position:

• chr11-32840107-A-G

Variant summary

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

The NM_024081.6(PRRG4):​c.317A>G​(p.Asp106Gly) variant causes a missense, splice region 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. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRRG4 NM_024081.6 missense, splice_region
• Scores: Splicing: ADA: 0.0005285
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26

Genes affected

PRRG4 (HGNC:30799): (proline rich and Gla domain 4) Enables WW domain binding activity. Located in plasma membrane. [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=0.13852316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRG4	NM_024081.6	c.317A>G	p.Asp106Gly	missense_variant, splice_region_variant	5/6	ENST00000257836.4	NP_076986.1
PRRG4	XM_006718314.4	c.317A>G	p.Asp106Gly	missense_variant, splice_region_variant	5/6		XP_006718377.1
PRRG4	XM_006718313.4	c.316+1177A>G		intron_variant			XP_006718376.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRG4	ENST00000257836.4	c.317A>G	p.Asp106Gly	missense_variant, splice_region_variant	5/6	1	NM_024081.6	ENSP00000257836.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

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

Mar 29, 2022

The c.317A>G (p.D106G) alteration is located in exon 5 (coding exon 4) of the PRRG4 gene. This alteration results from a A to G substitution at nucleotide position 317, causing the aspartic acid (D) at amino acid position 106 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	0.074
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.14	T
MetaSVM	Pathogenic	1.3	D
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.60	N
REVEL	Uncertain	0.39
Sift	Benign	0.42	T
Sift4G	Benign	0.50	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.25		Gain of glycosylation at S105 (P = 0.0308);
MVP		0.93
MPC		0.38
ClinPred		0.27	T
GERP RS		4.1
Varity_R		0.11
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00053
dbscSNV1_RF	Benign	0.026
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: rs1851063903; hg19: chr11-32861653;