rs17718511

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006846.4(SPINK5):​c.210-139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 733,196 control chromosomes in the GnomAD database, including 1,108 homozygotes. 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 0.034 ( 148 hom., cov: 32)
Exomes 𝑓: 0.045 ( 960 hom. )

Consequence

SPINK5
NM_006846.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.424
Variant links:
Genes affected
SPINK5 (HGNC:15464): (serine peptidase inhibitor Kazal type 5) This gene encodes a multidomain serine protease inhibitor that contains 15 potential inhibitory domains. The encoded preproprotein is proteolytically processed to generate multiple protein products, which may exhibit unique activities and specificities. These proteins may play a role in skin and hair morphogenesis, as well as anti-inflammatory and antimicrobial protection of mucous epithelia. Mutations in this gene may result in Netherton syndrome, a disorder characterized by ichthyosis, defective cornification, and atopy. This gene is present in a gene cluster on chromosome 5. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPINK5NM_006846.4 linkuse as main transcriptc.210-139A>G intron_variant ENST00000256084.8 NP_006837.2 Q9NQ38-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPINK5ENST00000256084.8 linkuse as main transcriptc.210-139A>G intron_variant 1 NM_006846.4 ENSP00000256084.7 Q9NQ38-1

Frequencies

GnomAD3 genomes
AF:
0.0338
AC:
5134
AN:
152004
Hom.:
148
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00702
Gnomad AMI
AF:
0.0143
Gnomad AMR
AF:
0.0536
Gnomad ASJ
AF:
0.0314
Gnomad EAS
AF:
0.125
Gnomad SAS
AF:
0.0668
Gnomad FIN
AF:
0.0573
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.0335
Gnomad OTH
AF:
0.0234
GnomAD4 exome
AF:
0.0452
AC:
26245
AN:
581074
Hom.:
960
AF XY:
0.0455
AC XY:
14180
AN XY:
311930
show subpopulations
Gnomad4 AFR exome
AF:
0.00626
Gnomad4 AMR exome
AF:
0.0534
Gnomad4 ASJ exome
AF:
0.0299
Gnomad4 EAS exome
AF:
0.165
Gnomad4 SAS exome
AF:
0.0615
Gnomad4 FIN exome
AF:
0.0527
Gnomad4 NFE exome
AF:
0.0335
Gnomad4 OTH exome
AF:
0.0346
GnomAD4 genome
AF:
0.0338
AC:
5140
AN:
152122
Hom.:
148
Cov.:
32
AF XY:
0.0366
AC XY:
2725
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00700
Gnomad4 AMR
AF:
0.0538
Gnomad4 ASJ
AF:
0.0314
Gnomad4 EAS
AF:
0.125
Gnomad4 SAS
AF:
0.0677
Gnomad4 FIN
AF:
0.0573
Gnomad4 NFE
AF:
0.0335
Gnomad4 OTH
AF:
0.0232
Alfa
AF:
0.0324
Hom.:
17
Bravo
AF:
0.0311
Asia WGS
AF:
0.0850
AC:
296
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
3.0
DANN
Benign
0.58

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: rs17718511; hg19: chr5-147451572; API