5-148088835-T-TAA

Position:

• chr5-148088835-T-TAA

Variant summary

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

The NM_006846.4(SPINK5):​c.474+240_474+241dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.023 (105 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-TAA is Benign according to our data. Variant chr5-148088835-T-TAA is described in ClinVar as [Benign]. Clinvar id is 1227062.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.474+240_474+241dupAA		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+240_474+241dupAA		intron_variant		1	NM_006846.4	ENSP00000256084.7

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3368 AN: 146360 Hom.: 105 Cov.: 0

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00765

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00282

Gnomad SAS AF: 0.000863

Gnomad FIN AF: 0.000861

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.000680

Gnomad OTH AF: 0.0147

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

GnomAD4 genome AF: 0.0230 AC: 3372 AN: 146438 Hom.: 105 Cov.: 0 AF XY: 0.0225 AC XY: 1606 AN XY: 71236

Gnomad4 AFR AF: 0.0788

Gnomad4 AMR AF: 0.00757

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00282

Gnomad4 SAS AF: 0.000867

Gnomad4 FIN AF: 0.000861

Gnomad4 NFE AF: 0.000680

Gnomad4 OTH AF: 0.0146

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

Nov 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;