chr5-147828056-A-G

Position:

• chr5-147828056-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001379610.1(SPINK1):​c.160T>C​(p.Tyr54His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPINK1 NM_001379610.1 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 4.35

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK1	NM_001379610.1	c.160T>C	p.Tyr54His	missense_variant	3/4	ENST00000296695.10	NP_001366539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK1	ENST00000296695.10	c.160T>C	p.Tyr54His	missense_variant	3/4	1	NM_001379610.1	ENSP00000296695.5
SPINK1	ENST00000510027.2	c.160T>C	p.Tyr54His	missense_variant	3/3	3		ENSP00000427376.1
SPINK1	ENST00000505722.1	n.75T>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Hereditary pancreatitis Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;.
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;T
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Pathogenic	0.95	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.82
MutPred		0.86		Gain of disorder (P = 0.068);Gain of disorder (P = 0.068);
MVP		0.81
MPC		0.17
ClinPred		1.0	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.92
gMVP		0.96

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: rs515726207; hg19: chr5-147207619;