6-35779401-C-T

Variant names:

• chr6-35779401-C-T
• rs1767918442
• NM_207409.4:c.254C>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.254C>T​(p.Thr85Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,433,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: CLPSL2 NM_207409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.07
• 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]

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=0.19008005).

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.254C>T	p.Thr85Met	missense	Exon 3 of 3	NP_997292.2	Q6UWE3-1
	CLPSL2	NM_001286550.2		c.333C>T	p.Asp111Asp	synonymous	Exon 4 of 4	NP_001273479.1	Q6UWE3-2
	CLPSL2	NR_104467.2		n.377C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPSL2	ENST00000403376.4	TSL:1 MANE Select	c.254C>T	p.Thr85Met	missense	Exon 3 of 3	ENSP00000385898.3	Q6UWE3-1
	CLPSL2	ENST00000360454.6	TSL:1	c.333C>T	p.Asp111Asp	synonymous	Exon 4 of 4	ENSP00000353639.2	Q6UWE3-2
	CLPSL2	ENST00000924056.1		c.131C>T	p.Thr44Met	missense	Exon 2 of 2	ENSP00000594115.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000698 AC: 10 AN: 1433040 Hom.: 0 Cov.: 31 AF XY: 0.00000704 AC XY: 5 AN XY: 709916

African (AFR) AF: 0.00 AC: 0 AN: 32952

American (AMR) AF: 0.00 AC: 0 AN: 40556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25540

East Asian (EAS) AF: 0.00 AC: 0 AN: 38554

South Asian (SAS) AF: 0.00 AC: 0 AN: 81834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00000912 AC: 10 AN: 1096850

Other (OTH) AF: 0.00 AC: 0 AN: 59398

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.97	T
PhyloP100		-3.1
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.13
MutPred		0.21		Gain of sheet (P = 0.0827)
MVP		0.030
MPC		0.30
ClinPred		0.51	D
GERP RS		-8.4
Varity_R		0.048
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1767918442; hg19: chr6-35747178;