6-35777480-C-T

Variant names:

• chr6-35777480-C-T
• NM_207409.4:c.106C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLPSL2 NM_207409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.590
• Publications: 0 publications found

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]

ENSG00000307849 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14746624).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207409.4. 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
	CLPSL2	NM_207409.4	MANE Select	c.106C>T	p.His36Tyr	missense	Exon 2 of 3	NP_997292.2	Q6UWE3-1
	CLPSL2	NM_001286550.2		c.106C>T	p.His36Tyr	missense	Exon 2 of 4	NP_001273479.1	Q6UWE3-2
	CLPSL2	NR_104467.2		n.229C>T		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPSL2	ENST00000403376.4	TSL:1 MANE Select	c.106C>T	p.His36Tyr	missense	Exon 2 of 3	ENSP00000385898.3	Q6UWE3-1
	CLPSL2	ENST00000360454.6	TSL:1	c.106C>T	p.His36Tyr	missense	Exon 2 of 4	ENSP00000353639.2	Q6UWE3-2
	CLPSL2	ENST00000924056.1		c.84+778C>T		intron	N/A	ENSP00000594115.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.59
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.32	B
Vest4		0.55
MutPred		0.39		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
Mutation Taster		=100/0	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

hg19: chr6-35745257;