NM_001370523.4:c.193C>T

Variant names:

• chr16-69952103-C-T
• rs1299024495
• NM_001370523.4:c.193C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001370523.4(CLEC18A):​c.193C>T​(p.Pro65Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000090 (0 hom., cov: 11)
  • Exomes 𝑓: 0.000073 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC18A NM_001370523.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17
• Publications: 0 publications found

Genes affected

CLEC18A (HGNC:30388): (C-type lectin domain family 18 member A) This is one of three closely related paralogous genes on chromosome 16 encoding secreted proteins containing C-type lectin domains. These domains bind to carbohydrates in the presence of calcium, and may be involved in cell adhesion, immune response and apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32645696).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370523.4. 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
	CLEC18A	NM_001370523.4	MANE Select	c.193C>T	p.Pro65Ser	missense	Exon 2 of 12	NP_001357452.1	A5D8T8-1
	CLEC18A	NM_001136214.4		c.193C>T	p.Pro65Ser	missense	Exon 3 of 13	NP_001129686.1	A5D8T8-1
	CLEC18A	NM_001271197.3		c.193C>T	p.Pro65Ser	missense	Exon 3 of 13	NP_001258126.1	A5D8T8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC18A	ENST00000288040.11	TSL:1 MANE Select	c.193C>T	p.Pro65Ser	missense	Exon 2 of 12	ENSP00000288040.6	A5D8T8-1
	CLEC18A	ENST00000393701.6	TSL:1	c.193C>T	p.Pro65Ser	missense	Exon 3 of 13	ENSP00000377304.2	A5D8T8-1
	CLEC18A	ENST00000568461.5	TSL:1	c.193C>T	p.Pro65Ser	missense	Exon 3 of 13	ENSP00000454685.1	A5D8T8-1

Frequencies

GnomAD3 genomes AF: 0.0000900 AC: 8 AN: 88900 Hom.: 0 Cov.: 11

Gnomad AFR AF: 0.0000912

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000112

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000733 AC: 37 AN: 505016 Hom.: 0 Cov.: 6 AF XY: 0.0000965 AC XY: 25 AN XY: 259050

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

African (AFR) AF: 0.0000785 AC: 1 AN: 12734

American (AMR) AF: 0.00 AC: 0 AN: 15766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12666

East Asian (EAS) AF: 0.00 AC: 0 AN: 23958

South Asian (SAS) AF: 0.000288 AC: 12 AN: 41724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1978

European-Non Finnish (NFE) AF: 0.0000725 AC: 24 AN: 331150

Other (OTH) AF: 0.00 AC: 0 AN: 26070

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000281508), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000900 AC: 8 AN: 88900 Hom.: 0 Cov.: 11 AF XY: 0.0000486 AC XY: 2 AN XY: 41182

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

African (AFR) AF: 0.0000912 AC: 2 AN: 21928

American (AMR) AF: 0.00 AC: 0 AN: 8334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2434

East Asian (EAS) AF: 0.00 AC: 0 AN: 2360

South Asian (SAS) AF: 0.000425 AC: 1 AN: 2352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.000112 AC: 5 AN: 44598

Other (OTH) AF: 0.00 AC: 0 AN: 1220

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000646934), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.2
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.090
Sift	Benign	0.088	T
Sift4G	Benign	0.12	T
Polyphen		0.96	D
Vest4		0.23
MutPred		0.73		Gain of MoRF binding (P = 0.0376)
MVP		0.27
MPC		2.1
ClinPred		0.88	D
GERP RS		0.096
PromoterAI		0.038	Neutral
Varity_R		0.14
gMVP		0.21
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1299024495; hg19: chr16-69986006;