5-148136632-G-C

Variant names:

• chr5-148136632-G-C
• rs4263489
• NM_006846.4:c.3187-351G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006846.4(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 NM_006846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 2 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)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.3187-351G>C		intron_variant	Intron 32 of 32	ENST00000256084.8	NP_006837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8	c.3187-351G>C		intron_variant	Intron 32 of 32	1	NM_006846.4	ENSP00000256084.7
SPINK5	ENST00000359874.7	c.3277-351G>C		intron_variant	Intron 33 of 33	1		ENSP00000352936.3
FBXO38-DT	ENST00000667608.1	n.1257-42890C>G		intron_variant	Intron 3 of 4

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

African (AFR) AF: 0.966 AC: 40134 AN: 41564

American (AMR) AF: 0.749 AC: 11422 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3156 AN: 3470

East Asian (EAS) AF: 0.861 AC: 4457 AN: 5174

South Asian (SAS) AF: 0.850 AC: 4102 AN: 4826

European-Finnish (FIN) AF: 0.910 AC: 9654 AN: 10612

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59171 AN: 68006

Other (OTH) AF: 0.884 AC: 1870 AN: 2116

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
PhyloP100		-2.5
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: rs4263489; hg19: chr5-147516195;