1-152972053-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173080.3(SPRR4):​c.163C>T​(p.Pro55Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SPRR4
NM_173080.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.211
Variant links:
Genes affected
SPRR4 (HGNC:23173): (small proline rich protein 4) Predicted to be involved in keratinization. Predicted to be located in cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.046810538).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPRR4NM_173080.3 linkc.163C>T p.Pro55Ser missense_variant Exon 2 of 2 ENST00000328051.3 NP_775103.1 Q96PI1
SPRR4XM_017000482.3 linkc.163C>T p.Pro55Ser missense_variant Exon 3 of 3 XP_016855971.1 Q96PI1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPRR4ENST00000328051.3 linkc.163C>T p.Pro55Ser missense_variant Exon 2 of 2 1 NM_173080.3 ENSP00000332163.2 Q96PI1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
Cov.:
31
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 31, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.163C>T (p.P55S) alteration is located in exon 2 (coding exon 1) of the SPRR4 gene. This alteration results from a C to T substitution at nucleotide position 163, causing the proline (P) at amino acid position 55 to be replaced by a serine (S). 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
0.083
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
2.3
DANN
Benign
0.57
DEOGEN2
Benign
0.054
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.46
T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.047
T
MetaSVM
Benign
-0.92
T
PROVEAN
Pathogenic
-6.3
D
REVEL
Benign
0.097
Sift
Benign
0.13
T
Sift4G
Benign
0.11
T
Polyphen
0.0060
B
Vest4
0.13
MutPred
0.10
Loss of catalytic residue at P55 (P = 2e-04);
MVP
0.093
MPC
0.0039
ClinPred
0.12
T
GERP RS
0.57
Varity_R
0.068
gMVP
0.0046

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-152944529; API