6-30561920-A-T

Variant names:

• chr6-30561920-A-T
• rs371325781
• NM_025263.4:c.256A>T

Variant summary

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

The NM_025263.4(PRR3):​c.256A>T​(p.Ile86Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I86V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PRR3 NM_025263.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

Genes affected

PRR3 (HGNC:21149): (proline rich 3) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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=0.042870015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR3	NM_025263.4	c.256A>T	p.Ile86Phe	missense_variant	Exon 3 of 4	ENST00000376560.8	NP_079539.2
PRR3	NM_001077497.3	c.193A>T	p.Ile65Phe	missense_variant	Exon 2 of 3		NP_001070965.1
PRR3	XM_047419381.1	c.*554A>T		downstream_gene_variant			XP_047275337.1
PRR3	XM_047419382.1	c.*554A>T		downstream_gene_variant			XP_047275338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR3	ENST00000376560.8	c.256A>T	p.Ile86Phe	missense_variant	Exon 3 of 4	1	NM_025263.4	ENSP00000365744.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460596 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 726608

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.3
DANN	Benign	0.92
DEOGEN2	Benign	0.0049	T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.068	N
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.13
Sift	Benign	0.15	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.090		Gain of methylation at R87 (P = 0.041);.;
MVP		0.15
MPC		0.56
ClinPred		0.032	T
GERP RS		-2.4
Varity_R		0.084
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs371325781; hg19: chr6-30529697;