5-148088835-T-TA

Variant names:

• chr5-148088835-T-TA
• rs397777404
• NM_006846.4:c.474+241dupA

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

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

LOC124901185 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.474+241dupA		intron_variant	Intron 6 of 32	ENST00000256084.8	NP_006837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8	c.474+241dupA		intron_variant	Intron 6 of 32	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

African (AFR) AF: 0.720 AC: 28870 AN: 40100

American (AMR) AF: 0.695 AC: 10189 AN: 14660

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2125 AN: 3404

East Asian (EAS) AF: 0.783 AC: 3882 AN: 4960

South Asian (SAS) AF: 0.779 AC: 3596 AN: 4616

European-Finnish (FIN) AF: 0.614 AC: 5696 AN: 9282

Middle Eastern (MID) AF: 0.689 AC: 197 AN: 286

European-Non Finnish (NFE) AF: 0.593 AC: 39223 AN: 66152

Other (OTH) AF: 0.681 AC: 1353 AN: 1986

Alfa AF: 0.381 Hom.: 591

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 03, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs397777404; hg19: chr5-147468398; COSMIC: COSV107188266; COSMIC: COSV107188266;