Variant chr5-148065222-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006846.4(SPINK5):c.56-125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 983,056 control chromosomes in the GnomAD database, including 186,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.60 ( 27343 hom., cov: 32)

Exomes 𝑓: 0.61 ( 159324 hom. )

Consequence

SPINK5
NM_006846.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.618

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 5-148065222-A-G is Benign according to our data. Variant chr5-148065222-A-G is described in ClinVar as [Benign]. Clinvar id is 1274357.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SPINK5	NM_006846.4 linkuse as main transcript	c.56-125A>G	intron_variant	ENST00000256084.8
SPINK5	NM_001127698.2 linkuse as main transcript	c.56-125A>G	intron_variant
SPINK5	NM_001127699.2 linkuse as main transcript	c.56-125A>G	intron_variant
SPINK5	XM_047416662.1 linkuse as main transcript	c.56-125A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINK5	ENST00000256084.8 linkuse as main transcript	c.56-125A>G		intron_variant		1	NM_006846.4	P2	Q9NQ38-1

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90505

AN:

151854

Hom.:

27347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.671

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.787

Gnomad SAS

AF:

0.788

Gnomad FIN

AF:

0.625

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.594

Gnomad OTH

AF:

0.630

GnomAD4 exome

AF:

0.613

AC:

509579

AN:

831084

Hom.:

159324

AF XY:

0.620

AC XY:

266860

AN XY:

430360

show subpopulations

Gnomad4 AFR exome

AF:

0.505

Gnomad4 AMR exome

AF:

0.743

Gnomad4 ASJ exome

AF:

0.640

Gnomad4 EAS exome

AF:

0.743

Gnomad4 SAS exome

AF:

0.779

Gnomad4 FIN exome

AF:

0.636

Gnomad4 NFE exome

AF:

0.580

Gnomad4 OTH exome

AF:

0.620

GnomAD4 genome

AF:

0.596

AC:

90528

AN:

151972

Hom.:

27343

Cov.:

AF XY:

0.604

AC XY:

44861

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.513

Gnomad4 AMR

AF:

0.672

Gnomad4 ASJ

AF:

0.630

Gnomad4 EAS

AF:

0.787

Gnomad4 SAS

AF:

0.787

Gnomad4 FIN

AF:

0.625

Gnomad4 NFE

AF:

0.594

Gnomad4 OTH

AF:

0.634

Alfa

AF:

0.574

Hom.:

3169

Bravo

AF:

0.597

Asia WGS

AF:

0.773

AC:

2680

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.64

DANN

Benign

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over