rs2766597

Variant names:

• chr6-35797266-A-C
• NM_001832.4:c.23T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-35797266-A-C
• chr6-35797266-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001832.4(CLPS):​c.23T>G​(p.Leu8Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,402 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L8P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 44)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLPS NM_001832.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.51

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]

LHFPL5 (HGNC:21253): (LHFPL tetraspan subfamily member 5) This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. Mutations in this gene result in deafness in humans, and a mutation in a similar gene in mice results in deafness and vestibular dysfunction with severe degeneration of the organ of Corti. It is proposed to function in hair bundle morphogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPS	NM_001832.4	c.23T>G	p.Leu8Arg	missense_variant	Exon 1 of 3	ENST00000259938.7	NP_001823.1
CLPS	NM_001252598.2	c.23T>G	p.Leu8Arg	missense_variant	Exon 1 of 2		NP_001239527.1
CLPS	NM_001252597.2	c.-118T>G		5_prime_UTR_variant	Exon 1 of 4		NP_001239526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPS	ENST00000259938.7	c.23T>G	p.Leu8Arg	missense_variant	Exon 1 of 3	1	NM_001832.4	ENSP00000259938.2
CLPS	ENST00000616014.3	c.23T>G	p.Leu8Arg	missense_variant	Exon 1 of 2	1		ENSP00000483589.1
LHFPL5	ENST00000651132	c.-346A>C		5_prime_UTR_variant	Exon 1 of 7			ENSP00000498322.1

Frequencies

GnomAD3 genomes Cov.: 44

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461402 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 44

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.1	D;.
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.99	D;.
Vest4		0.53
MutPred		0.60		Loss of stability (P = 0.026);Loss of stability (P = 0.026);
MVP		0.61
MPC		1.3
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.77
gMVP		0.83

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: chr6-35765043;