chr2-27137260-G-A

Position:

• chr2-27137260-G-A

Variant summary

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

The NM_178553.4(PRR30):​c.1070C>T​(p.Thr357Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRR30 NM_178553.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.151

Genes affected

PRR30 (HGNC:28677): (proline rich 30)

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=0.098035514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR30	NM_178553.4	c.1070C>T	p.Thr357Ile	missense_variant	3/3	ENST00000335524.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR30	ENST00000335524.7	c.1070C>T	p.Thr357Ile	missense_variant	3/3	1	NM_178553.4	P1
PRR30	ENST00000432962.2	c.576C>T	p.Asp192=	synonymous_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Sep 29, 2022

The c.1070C>T (p.T357I) alteration is located in exon 3 (coding exon 1) of the PRR30 gene. This alteration results from a C to T substitution at nucleotide position 1070, causing the threonine (T) at amino acid position 357 to be replaced by an isoleucine (I). 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	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.061
Sift	Benign	0.10	T
Sift4G	Benign	0.10	T
Polyphen		0.90	P
Vest4		0.071
MutPred		0.17		Loss of phosphorylation at T357 (P = 0.0106);
MVP		0.17
MPC		0.32
ClinPred		0.40	T
GERP RS		2.6
Varity_R		0.050
gMVP		0.093

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: rs969681333; hg19: chr2-27360128;