6-35787903-C-T

Variant names:

• chr6-35787903-C-T
• rs201083630
• NM_001010886.5:c.259C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001010886.5(CLPSL1):​c.259C>T​(p.Arg87Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,606,962 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 40)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: CLPSL1 NM_001010886.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.315
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04101321).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010886.5. 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
	CLPSL1	NM_001010886.5	MANE Select	c.259C>T	p.Arg87Trp	missense	Exon 3 of 3	NP_001010886.1	A2RUU4
	CLPSL1	NM_001348773.2		c.222+783C>T		intron	N/A	NP_001335702.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPSL1	ENST00000373861.6	TSL:1 MANE Select	c.259C>T	p.Arg87Trp	missense	Exon 3 of 3	ENSP00000362968.5	A2RUU4
	CLPSL1	ENST00000428710.1	TSL:3	c.81+783C>T		intron	N/A	ENSP00000396556.1	Q5T9G0

Frequencies

GnomAD3 genomes AF: 0.000144 AC: 22 AN: 152258 Hom.: 0 Cov.: 40

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000232 AC: 58 AN: 249550 AF XY: 0.000295

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000180 AC: 262 AN: 1454704 Hom.: 2 Cov.: 32 AF XY: 0.000210 AC XY: 152 AN XY: 724092

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000900 AC: 3 AN: 33320

American (AMR) AF: 0.0000671 AC: 3 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39628

South Asian (SAS) AF: 0.00110 AC: 95 AN: 86070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5748

European-Non Finnish (NFE) AF: 0.0000941 AC: 104 AN: 1105670

Other (OTH) AF: 0.000665 AC: 40 AN: 60142

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152258 Hom.: 0 Cov.: 40 AF XY: 0.000148 AC XY: 11 AN XY: 74388

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000482 AC: 2 AN: 41468

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000000531797), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000176 Hom.: 0

ESP6500AA AF: 0.000247 AC: 1

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.000198 AC: 24

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000119

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	0.092
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.32
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.13
MVP		0.17
MPC		0.021
ClinPred		0.089	T
GERP RS		0.81
Varity_R		0.086
gMVP		0.42
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs201083630; hg19: chr6-35755680;