dbSNP rs28989168: SPRR3:p.Gly73Gly (chr1-153003239-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001097589.2(SPRR3):c.219C>A(p.Gly73Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPRR3
NM_001097589.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.147

Publications

17 publications found

Variant links:

Genes affected

SPRR3 (HGNC:11268): (small proline rich protein 3) Predicted to enable structural molecule activity. Predicted to be involved in wound healing. Located in Golgi apparatus and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPRR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=-0.147 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRR3	NM_001097589.2 link	c.219C>A	p.Gly73Gly	synonymous_variant	Exon 2 of 2	ENST00000295367.5	NP_001091058.1	Q9UBC9
SPRR3	NM_005416.3 link	c.219C>A	p.Gly73Gly	synonymous_variant	Exon 3 of 3		NP_005407.1	Q9UBC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPRR3	ENST00000295367.5 link	c.219C>A	p.Gly73Gly	synonymous_variant	Exon 2 of 2	1	NM_001097589.2	ENSP00000295367.4	Q9UBC9
SPRR3	ENST00000331860.7 link	c.219C>A	p.Gly73Gly	synonymous_variant	Exon 3 of 3	3		ENSP00000330391.3	Q9UBC9
SPRR3	ENST00000443178.1 link	c.219C>A	p.Gly73Gly	synonymous_variant	Exon 3 of 3	3		ENSP00000402016.1	B1AN48

Frequencies

GnomAD3 genomes

AF:

0.0000327

AC:

AN:

30552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000824

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:

0.00000132

AC:

AN:

758268

Hom.:

Cov.:

AF XY:

0.00000256

AC XY:

AN XY:

391010

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15702

American (AMR)

AF:

0.00

AC:

AN:

26926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17414

East Asian (EAS)

AF:

0.00

AC:

AN:

32098

South Asian (SAS)

AF:

0.00

AC:

AN:

57402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3992

European-Non Finnish (NFE)

AF:

0.00000192

AC:

AN:

521534

Other (OTH)

AF:

0.00

AC:

AN:

35704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000327

AC:

AN:

30552

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

15144

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

4394

American (AMR)

AF:

0.00

AC:

AN:

3982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

772

East Asian (EAS)

AF:

0.00

AC:

AN:

738

South Asian (SAS)

AF:

0.000824

AC:

AN:

1214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

15854

Other (OTH)

AF:

0.00

AC:

AN:

416

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.91

(source)

DANN

Benign

0.31

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over