dbSNP rs2052537: SPINK5:c.2667-13A>C (chr5-148124752-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006846.4(SPINK5):c.2667-13A>C variant causes a intron 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 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPINK5
NM_006846.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

Publications

4 publications found

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]

SPINK5 links:

FBXO38-DT (HGNC:55589): (FBXO38 divergent transcript)

FBXO38-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK5	NM_006846.4 link	c.2667-13A>C		intron_variant	Intron 27 of 32	ENST00000256084.8	NP_006837.2	Q9NQ38-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPINK5	ENST00000256084.8 link	c.2667-13A>C	intron_variant	Intron 27 of 32	1	NM_006846.4	ENSP00000256084.7	Q9NQ38-1
SPINK5	ENST00000359874.7 link	c.2667-13A>C	intron_variant	Intron 27 of 33	1		ENSP00000352936.3	Q9NQ38-3
SPINK5	ENST00000398454.5 link	c.2667-13A>C	intron_variant	Intron 27 of 27	1		ENSP00000381472.1	Q9NQ38-2
FBXO38-DT	ENST00000667608.1 link	n.1257-31010T>G	intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150838

Hom.:

Cov.:

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:

0.00

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: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1380024

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683604

African (AFR)

AF:

0.00

AC:

AN:

29818

American (AMR)

AF:

0.00

AC:

AN:

33930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23780

East Asian (EAS)

AF:

0.00

AC:

AN:

36994

South Asian (SAS)

AF:

0.00

AC:

AN:

70612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4970

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1073256

Other (OTH)

AF:

0.00

AC:

AN:

56628

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

150838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73520

African (AFR)

AF:

0.00

AC:

AN:

41120

American (AMR)

AF:

0.00

AC:

AN:

15140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67626

Other (OTH)

AF:

0.00

AC:

AN:

2074

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.3

(source)

DANN

Benign

0.16

PhyloP100

-0.066

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over