rs17107315

Variant names:

• chr5-147828115-T-A
• NM_001379610.1:c.101A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-147828115-T-A
• chr5-147828115-T-C
• chr5-147828115-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_001379610.1(SPINK1):​c.101A>T​(p.Asn34Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N34S) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPINK1 NM_001379610.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr5-147828115-T-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.17723742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK1	NM_001379610.1	c.101A>T	p.Asn34Ile	missense_variant	Exon 3 of 4	ENST00000296695.10	NP_001366539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK1	ENST00000296695.10	c.101A>T	p.Asn34Ile	missense_variant	Exon 3 of 4	1	NM_001379610.1	ENSP00000296695.5
SPINK1	ENST00000510027.2	c.101A>T	p.Asn34Ile	missense_variant	Exon 3 of 3	3		ENSP00000427376.1
SPINK1	ENST00000505722.1	n.16A>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.0030
DANN	Benign	0.59
DEOGEN2	Benign	0.28	T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.81	T
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.24
Sift	Benign	0.085	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.76	P;.
Vest4		0.31
MutPred		0.55		Loss of ubiquitination at K31 (P = 0.0421);Loss of ubiquitination at K31 (P = 0.0421);
MVP		0.44
MPC		0.027
ClinPred		0.42	T
GERP RS		-3.9
Varity_R		0.35
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-147207678;