1-153040177-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006945.5(SPRR2D):​c.170T>G​(p.Val57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,612,990 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: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

SPRR2D
NM_006945.5 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.656
Variant links:
Genes affected
SPRR2D (HGNC:11264): (small proline rich protein 2D) Predicted to be involved in keratinization. Predicted to act upstream of or within female gonad development and response to estradiol. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13569057).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPRR2DNM_006945.5 linkc.170T>G p.Val57Gly missense_variant Exon 2 of 2 ENST00000360379.4 NP_008876.3 P22532
SPRR2DNM_001382248.1 linkc.170T>G p.Val57Gly missense_variant Exon 2 of 2 NP_001369177.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPRR2DENST00000360379.4 linkc.170T>G p.Val57Gly missense_variant Exon 2 of 2 1 NM_006945.5 ENSP00000353542.3 P22532
SPRR2DENST00000368756.1 linkc.170T>G p.Val57Gly missense_variant Exon 3 of 3 2 ENSP00000357745.1 P22532
SPRR2DENST00000368757.1 linkc.170T>G p.Val57Gly missense_variant Exon 2 of 2 3 ENSP00000357746.1 P22532
SPRR2DENST00000368758.3 linkc.170T>G p.Val57Gly missense_variant Exon 2 of 2 2 ENSP00000357747.3 P22532

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152110
Hom.:
0
Cov.:
32
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:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000836
AC:
21
AN:
251116
Hom.:
0
AF XY:
0.000111
AC XY:
15
AN XY:
135698
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000970
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000541
AC:
79
AN:
1460762
Hom.:
0
Cov.:
31
AF XY:
0.0000605
AC XY:
44
AN XY:
726724
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000549
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152228
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000831
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000273
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 14, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.170T>G (p.V57G) alteration is located in exon 2 (coding exon 1) of the SPRR2D gene. This alteration results from a T to G substitution at nucleotide position 170, causing the valine (V) at amino acid position 57 to be replaced by a glycine (G). 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
0.15
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
16
DANN
Benign
0.78
DEOGEN2
Benign
0.036
T;T;T;T
Eigen
Benign
-0.033
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.27
.;.;.;T
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-0.88
T
PROVEAN
Uncertain
-3.5
D;D;D;D
REVEL
Benign
0.17
Sift4G
Benign
0.56
T;T;T;T
Polyphen
0.99
D;D;D;D
Vest4
0.35
MVP
0.49
MPC
0.62
ClinPred
0.74
D
GERP RS
3.4
Varity_R
0.64
gMVP
0.0024

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148544013; hg19: chr1-153012653; COSMIC: COSV64209023; API