5-148088835-T-TA

Position:

• chr5-148088835-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006846.4(SPINK5):​c.474+241dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (31158 hom., cov: 0)
• Consequence: SPINK5 NM_006846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.20

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-148088835-T-TA is Benign according to our data. Variant chr5-148088835-T-TA is described in ClinVar as [Benign]. Clinvar id is 1292838.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.474+241dupA		intron_variant		ENST00000256084.8	NP_006837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8	c.474+241dupA		intron_variant		1	NM_006846.4	ENSP00000256084.7

Frequencies

GnomAD3 genomes AF: 0.654 AC: 95598 AN: 146272 Hom.: 31158 Cov.: 0

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.679

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.653 AC: 95632 AN: 146350 Hom.: 31158 Cov.: 0 AF XY: 0.659 AC XY: 46878 AN XY: 71164

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.681

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs397777404; hg19: chr5-147468398;