1-153003239-C-T

Variant names:

• chr1-153003239-C-T
• rs28989168
• NM_001097589.2:c.219C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001097589.2(SPRR3):​c.219C>T​(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 0.0015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.027 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPRR3 NM_001097589.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 17 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.147 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001097589.2. 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
	SPRR3	NM_001097589.2	MANE Select	c.219C>T	p.Gly73Gly	synonymous	Exon 2 of 2	NP_001091058.1
	SPRR3	NM_005416.3		c.219C>T	p.Gly73Gly	synonymous	Exon 3 of 3	NP_005407.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRR3	ENST00000295367.5	TSL:1 MANE Select	c.219C>T	p.Gly73Gly	synonymous	Exon 2 of 2	ENSP00000295367.4
	SPRR3	ENST00000331860.7	TSL:3	c.219C>T	p.Gly73Gly	synonymous	Exon 3 of 3	ENSP00000330391.3
	SPRR3	ENST00000443178.1	TSL:3	c.219C>T	p.Gly73Gly	synonymous	Exon 3 of 3	ENSP00000402016.1

Frequencies

GnomAD3 genomes AF: 0.00151 AC: 46 AN: 30528 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00617

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000753

Gnomad ASJ AF: 0.00130

Gnomad EAS AF: 0.00542

Gnomad SAS AF: 0.00412

Gnomad FIN AF: 0.000360

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000316

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000633 AC: 112 AN: 176836 AF XY: 0.000696

Gnomad AFR exome AF: 0.0000983

Gnomad AMR exome AF: 0.000169

Gnomad ASJ exome AF: 0.00144

Gnomad EAS exome AF: 0.0000977

Gnomad FIN exome AF: 0.000409

Gnomad NFE exome AF: 0.000749

Gnomad OTH exome AF: 0.000516

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0274 AC: 20489 AN: 747626 Hom.: 1 Cov.: 30 AF XY: 0.0258 AC XY: 9960 AN XY: 385366

African (AFR) AF: 0.0443 AC: 688 AN: 15540

American (AMR) AF: 0.00280 AC: 75 AN: 26798

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 281 AN: 17106

East Asian (EAS) AF: 0.00371 AC: 119 AN: 32074

South Asian (SAS) AF: 0.0116 AC: 655 AN: 56500

European-Finnish (FIN) AF: 0.00156 AC: 74 AN: 47318

Middle Eastern (MID) AF: 0.00987 AC: 39 AN: 3952

European-Non Finnish (NFE) AF: 0.0347 AC: 17815 AN: 512932

Other (OTH) AF: 0.0210 AC: 743 AN: 35406

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00151 AC: 46 AN: 30524 Hom.: 0 Cov.: 0 AF XY: 0.00185 AC XY: 28 AN XY: 15144

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

African (AFR) AF: 0.00617 AC: 27 AN: 4374

American (AMR) AF: 0.000752 AC: 3 AN: 3988

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 1 AN: 772

East Asian (EAS) AF: 0.00542 AC: 4 AN: 738

South Asian (SAS) AF: 0.00413 AC: 5 AN: 1212

European-Finnish (FIN) AF: 0.000360 AC: 1 AN: 2778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 84

European-Non Finnish (NFE) AF: 0.000315 AC: 5 AN: 15848

Other (OTH) AF: 0.00 AC: 0 AN: 422

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000000888178), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000776 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.29
PhyloP100		-0.15
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: rs28989168; hg19: chr1-152975715; COSMIC: COSV54878285; COSMIC: COSV54878285;