5-147828151-T-G

Variant names:

• chr5-147828151-T-G
• rs199929811
• NM_001379610.1:c.88-23A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001379610.1(SPINK1):​c.88-23A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,409,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPINK1 NM_001379610.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915
• Publications: 3 publications found

Genes affected

SPINK1 (HGNC:11244): (serine peptidase inhibitor Kazal type 1) The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis. [provided by RefSeq, Oct 2008]

SPINK1 Gene-Disease associations (from GenCC):

• hereditary chronic pancreatitis

  Inheritance: AD, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, NO_KNOWN Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379610.1. 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
	SPINK1	NM_001379610.1	MANE Select	c.88-23A>C		intron	N/A	NP_001366539.1	P00995
	SPINK1	NM_001354966.2		c.88-23A>C		intron	N/A	NP_001341895.1	P00995
	SPINK1	NM_003122.5		c.88-23A>C		intron	N/A	NP_003113.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK1	ENST00000296695.10	TSL:1 MANE Select	c.88-23A>C		intron	N/A	ENSP00000296695.5	P00995
	SPINK1	ENST00000510027.2	TSL:3	c.88-23A>C		intron	N/A	ENSP00000427376.1	D6RIU5
	SPINK1	ENST00000505722.1	TSL:2	n.-21A>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000418 AC: 1 AN: 239486 AF XY: 0.00000772

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000937

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1409316 Hom.: 0 Cov.: 22 AF XY: 0.00000142 AC XY: 1 AN XY: 703784

African (AFR) AF: 0.00 AC: 0 AN: 32390

American (AMR) AF: 0.00 AC: 0 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25712

East Asian (EAS) AF: 0.00 AC: 0 AN: 39154

South Asian (SAS) AF: 0.00 AC: 0 AN: 84466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1067144

Other (OTH) AF: 0.00 AC: 0 AN: 58568

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		0.92
La Branchor		0.60
BranchPoint Hunter		0.0

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: rs199929811; hg19: chr5-147207714;