6-35787078-C-G

Variant names:

• chr6-35787078-C-G
• NM_001010886.5:c.180C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010886.5(CLPSL1):​c.180C>G​(p.His60Gln) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 41)
• Consequence: CLPSL1 NM_001010886.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.360

Genes affected

CLPSL1 (HGNC:21251): (colipase like 1) Predicted to enable enzyme activator activity. Predicted to be involved in response to food. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11880791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPSL1	NM_001010886.5	c.180C>G	p.His60Gln	missense_variant	Exon 2 of 3	ENST00000373861.6	NP_001010886.1
CLPSL1	NM_001348773.2	c.180C>G	p.His60Gln	missense_variant	Exon 2 of 3		NP_001335702.1
CLPSL1	XM_017010820.2	c.192C>G	p.His64Gln	missense_variant	Exon 1 of 2		XP_016866309.1
CLPSL1	XM_017010821.2	c.192C>G	p.His64Gln	missense_variant	Exon 1 of 2		XP_016866310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPSL1	ENST00000373861.6	c.180C>G	p.His60Gln	missense_variant	Exon 2 of 3	1	NM_001010886.5	ENSP00000362968.5
CLPSL1	ENST00000428710.1	c.39C>G	p.His13Gln	missense_variant	Exon 1 of 2	3		ENSP00000396556.1

Frequencies

GnomAD3 genomes Cov.: 41

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 41

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.180C>G (p.H60Q) alteration is located in exon 2 (coding exon 2) of the CLPSL1 gene. This alteration results from a C to G substitution at nucleotide position 180, causing the histidine (H) at amino acid position 60 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.81
DEOGEN2	Benign	0.042	T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N;D
REVEL	Benign	0.018
Sift	Benign	0.16	T;.
Sift4G	Uncertain	0.031	D;T
Polyphen		0.22	B;.
Vest4		0.33
MutPred		0.25		Gain of helix (P = 0.062);.;
MVP		0.061
MPC		0.14
ClinPred		0.13	T
GERP RS		-0.94
Varity_R		0.066
gMVP		0.38

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-35754855;