rs2052537

Variant names:

• chr5-148124752-A-G
• rs2052537
• NM_006846.4:c.2667-13A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-148124752-A-G
• chr5-148124752-A-T
• chr5-148124752-A-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006846.4(SPINK5):​c.2667-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,530,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: SPINK5 NM_006846.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660
• Publications: 4 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-148124752-A-G is Benign according to our data. Variant chr5-148124752-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3626948.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK5	NM_006846.4	MANE Select	c.2667-13A>G		intron	N/A	NP_006837.2	Q9NQ38-1
	SPINK5	NM_001127698.2		c.2667-13A>G		intron	N/A	NP_001121170.1	Q9NQ38-3
	SPINK5	NM_001127699.2		c.2667-13A>G		intron	N/A	NP_001121171.1	Q9NQ38-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK5	ENST00000256084.8	TSL:1 MANE Select	c.2667-13A>G		intron	N/A	ENSP00000256084.7	Q9NQ38-1
	SPINK5	ENST00000359874.7	TSL:1	c.2667-13A>G		intron	N/A	ENSP00000352936.3	Q9NQ38-3
	SPINK5	ENST00000398454.5	TSL:1	c.2667-13A>G		intron	N/A	ENSP00000381472.1	Q9NQ38-2

Frequencies

GnomAD3 genomes AF: 0.0000398 AC: 6 AN: 150838 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000725 AC: 10 AN: 1380030 Hom.: 0 Cov.: 25 AF XY: 0.00000439 AC XY: 3 AN XY: 683608

African (AFR) AF: 0.000268 AC: 8 AN: 29818

American (AMR) AF: 0.0000295 AC: 1 AN: 33930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23780

East Asian (EAS) AF: 0.00 AC: 0 AN: 36994

South Asian (SAS) AF: 0.00 AC: 0 AN: 70612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4970

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073262

Other (OTH) AF: 0.0000177 AC: 1 AN: 56628

GnomAD4 genome AF: 0.0000398 AC: 6 AN: 150838 Hom.: 0 Cov.: 29 AF XY: 0.0000408 AC XY: 3 AN XY: 73520

African (AFR) AF: 0.000146 AC: 6 AN: 41120

American (AMR) AF: 0.00 AC: 0 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67626

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 626

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Ichthyosis linearis circumflexa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.48
PhyloP100		-0.066

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: rs2052537; hg19: chr5-147504315;