chr12-11267980-T-C

Variant names:

• chr12-11267980-T-C
• rs1948611412
• NM_001394862.1:c.269A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001394862.1(PRB3):​c.269A>G​(p.Gln90Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000072 (0 hom., cov: 19)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRB3 NM_001394862.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.977
• Publications: 0 publications found

Genes affected

PRB3 (HGNC:9339): (proline rich protein BstNI subfamily 3) This gene encodes a member of the heterogeneous family of basic, proline-rich, human salivary glycoproteins. Multiple alleles of this gene exhibiting variations in the length of the tandem repeats have been identified. The reference genome encodes the "Long" allele. The protein isoforms encoded by this gene are recognized as the "first line of oral defense" against the detrimental effects of polyphenols in the diet and pathogen infections. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. [provided by RefSeq, Nov 2015]

LOC107987435 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07611281).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394862.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRB3	NM_001394862.1	MANE Select	c.269A>G	p.Gln90Arg	missense	Exon 3 of 4	NP_001381791.1	Q04118
	PRB3	NM_006249.5		c.269A>G	p.Gln90Arg	missense	Exon 3 of 5	NP_006240.4	A0A0G2JNB4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRB3	ENST00000538488.3	TSL:5 MANE Select	c.269A>G	p.Gln90Arg	missense	Exon 3 of 4	ENSP00000442626.2	Q04118
	PRB3	ENST00000539835.1	TSL:2	n.276A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00000720 AC: 1 AN: 138972 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000708

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.93e-7 AC: 1 AN: 1443774 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 718066

African (AFR) AF: 0.00 AC: 0 AN: 33148

American (AMR) AF: 0.00 AC: 0 AN: 44128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25328

East Asian (EAS) AF: 0.00 AC: 0 AN: 39396

South Asian (SAS) AF: 0.00 AC: 0 AN: 85410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099480

Other (OTH) AF: 0.0000169 AC: 1 AN: 59300

GnomAD4 genome AF: 0.00000720 AC: 1 AN: 138972 Hom.: 0 Cov.: 19 AF XY: 0.0000148 AC XY: 1 AN XY: 67498

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 35730

American (AMR) AF: 0.0000708 AC: 1 AN: 14134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3364

East Asian (EAS) AF: 0.00 AC: 0 AN: 4622

South Asian (SAS) AF: 0.00 AC: 0 AN: 4074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64608

Other (OTH) AF: 0.00 AC: 0 AN: 1916

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.1
DANN	Benign	0.86
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0032	N
M_CAP	Benign	0.00049	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.93	T
PhyloP100		0.98
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.016
Sift4G	Benign	0.53	T
Vest4		0.21
MutPred		0.33		Gain of catalytic residue at P93 (P = 3e-04)
MVP		0.030
MPC		0.36
ClinPred		0.096	T
GERP RS		-1.2
gMVP		0.074
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1948611412; hg19: chr12-11420914;