6-35795835-T-A

Variant names:

• chr6-35795835-T-A
• rs760509453
• NM_001832.4:c.103A>T

Variant summary

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

The NM_001832.4(CLPS):​c.103A>T​(p.Met35Leu) 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. 16/22 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. M35V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 40)
• Consequence: CLPS NM_001832.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.23
• Publications: 0 publications found

Genes affected

CLPS (HGNC:2085): (colipase) The protein encoded by this gene is a cofactor needed by pancreatic lipase for efficient dietary lipid hydrolysis. It binds to the C-terminal, non-catalytic domain of lipase, thereby stabilizing an active conformation and considerably increasing the overall hydrophobic binding site. The gene product allows lipase to anchor noncovalently to the surface of lipid micelles, counteracting the destabilizing influence of intestinal bile salts. This cofactor is only expressed in pancreatic acinar cells, suggesting regulation of expression by tissue-specific elements. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05186072).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001832.4. 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
	CLPS	NM_001832.4	MANE Select	c.103A>T	p.Met35Leu	missense	Exon 2 of 3	NP_001823.1	P04118
	CLPS	NM_001252597.2		c.61A>T	p.Met21Leu	missense	Exon 3 of 4	NP_001239526.1	A0A087WZW1
	CLPS	NM_001252598.2		c.85-558A>T		intron	N/A	NP_001239527.1	A0A087X0Q7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPS	ENST00000259938.7	TSL:1 MANE Select	c.103A>T	p.Met35Leu	missense	Exon 2 of 3	ENSP00000259938.2	P04118
	CLPS	ENST00000616014.3	TSL:1	c.85-558A>T		intron	N/A	ENSP00000483589.1	A0A087X0Q7
	CLPS	ENST00000912425.1		c.103A>T	p.Met35Leu	missense	Exon 3 of 4	ENSP00000582484.1

Frequencies

GnomAD3 genomes Cov.: 40

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 40

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0010
DANN	Benign	0.73
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.52	N
PhyloP100		-4.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.038
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.32		Loss of helix (P = 0.1299)
MVP		0.11
MPC		0.34
ClinPred		0.063	T
GERP RS		-10
Varity_R		0.069
gMVP		0.43
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs760509453; hg19: chr6-35763612;