chr6-35777480-C-T

Position:

• chr6-35777480-C-T

Variant summary

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

The NM_207409.4(CLPSL2):​c.106C>T​(p.His36Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLPSL2 NM_207409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.590

Genes affected

CLPSL2 (HGNC:21250): (colipase like 2) 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]

CLPSL2 (HGNC:):

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=0.14746624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPSL2	NM_207409.4	c.106C>T	p.His36Tyr	missense_variant	2/3	ENST00000403376.4	NP_997292.2
CLPSL2	NM_001286550.2	c.106C>T	p.His36Tyr	missense_variant	2/4		NP_001273479.1
CLPSL2	NR_104467.2	n.229C>T		non_coding_transcript_exon_variant	2/3
CLPSL2	NR_104469.2	n.207+676C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPSL2	ENST00000403376.4	c.106C>T	p.His36Tyr	missense_variant	2/3	1	NM_207409.4	ENSP00000385898.3
CLPSL2	ENST00000360454.6	c.106C>T	p.His36Tyr	missense_variant	2/4	1		ENSP00000353639.2
CLPSL2	ENST00000481904.5	n.233C>T		non_coding_transcript_exon_variant	2/3	3
CLPSL2	ENST00000467122.1	n.115+676C>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.106C>T (p.H36Y) alteration is located in exon 2 (coding exon 2) of the CLPSL2 gene. This alteration results from a C to T substitution at nucleotide position 106, causing the histidine (H) at amino acid position 36 to be replaced by a tyrosine (Y). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.0000018	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.084	.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.32	B;B
Vest4		0.55
MutPred		0.39		Loss of disorder (P = 0.1598);Loss of disorder (P = 0.1598);
MVP		0.014
MPC		0.19
ClinPred		0.81	D
GERP RS		1.6
Varity_R		0.36
gMVP		0.10

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: chr6-35745257;