5-148136632-G-C

Position:

• chr5-148136632-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000256084.8(SPINK5):​c.3187-351G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,226 control chromosomes in the GnomAD database, including 60,256 homozygotes. 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 0.89 (60256 hom., cov: 32)
• Consequence: SPINK5 ENST00000256084.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.3187-351G>C		intron_variant		ENST00000256084.8	NP_006837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8	c.3187-351G>C		intron_variant		1	NM_006846.4	ENSP00000256084	P2
SPINK5	ENST00000359874.7	c.3277-351G>C		intron_variant		1		ENSP00000352936	A2
FBXO38-DT	ENST00000667608.1	n.1257-42890C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134917 AN: 152108 Hom.: 60204 Cov.: 32

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.885

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

GnomAD4 genome AF: 0.887 AC: 135024 AN: 152226 Hom.: 60256 Cov.: 32 AF XY: 0.885 AC XY: 65847 AN XY: 74430

Gnomad4 AFR AF: 0.966

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.910

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.884

Alfa AF: 0.880 Hom.: 6891

Bravo AF: 0.876

Asia WGS AF: 0.855 AC: 2975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
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

Other links and lift over

dbSNP: rs4263489; hg19: chr5-147516195;