5-148078376-G-C

Position:

• chr5-148078376-G-C

Variant summary

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

The NM_006846.4(SPINK5):​c.282+6156G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 150,734 control chromosomes in the GnomAD database, including 43,223 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 0.75 (43223 hom., cov: 30)
• Consequence: SPINK5 NM_006846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.282+6156G>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.282+6156G>C		intron_variant		1	NM_006846.4	ENSP00000256084	P2

Frequencies

GnomAD3 genomes AF: 0.746 AC: 112342 AN: 150618 Hom.: 43172 Cov.: 30

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.746 AC: 112452 AN: 150734 Hom.: 43223 Cov.: 30 AF XY: 0.753 AC XY: 55451 AN XY: 73650

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.740

Alfa AF: 0.559 Hom.: 1647

Bravo AF: 0.761

Asia WGS AF: 0.881 AC: 3027 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.97
DANN	Benign	0.42

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: rs4357026; hg19: chr5-147457939;