NM_001370523.4:c.197C>T

Variant names:

• chr16-69952107-C-T
• rs1344888245
• NM_001370523.4:c.197C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001370523.4(CLEC18A):​c.197C>T​(p.Ala66Val) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000022 (0 hom., cov: 12)
  • Exomes 𝑓: 0.000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC18A NM_001370523.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.51
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.955

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.197C>T	p.Ala66Val	missense	Exon 2 of 12	NP_001357452.1	A5D8T8-1
	CLEC18A	NM_001136214.4		c.197C>T	p.Ala66Val	missense	Exon 3 of 13	NP_001129686.1	A5D8T8-1
	CLEC18A	NM_001271197.3		c.197C>T	p.Ala66Val	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.197C>T	p.Ala66Val	missense	Exon 2 of 12	ENSP00000288040.6	A5D8T8-1
	CLEC18A	ENST00000393701.6	TSL:1	c.197C>T	p.Ala66Val	missense	Exon 3 of 13	ENSP00000377304.2	A5D8T8-1
	CLEC18A	ENST00000568461.5	TSL:1	c.197C>T	p.Ala66Val	missense	Exon 3 of 13	ENSP00000454685.1	A5D8T8-1

Frequencies

GnomAD3 genomes AF: 0.0000225 AC: 2 AN: 89044 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.0000913

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000124 AC: 6 AN: 485410 Hom.: 0 Cov.: 6 AF XY: 0.00000802 AC XY: 2 AN XY: 249312

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

African (AFR) AF: 0.000162 AC: 2 AN: 12358

American (AMR) AF: 0.00 AC: 0 AN: 15316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12338

East Asian (EAS) AF: 0.00 AC: 0 AN: 23358

South Asian (SAS) AF: 0.0000248 AC: 1 AN: 40376

European-Finnish (FIN) AF: 0.0000261 AC: 1 AN: 38342

Middle Eastern (MID) AF: 0.000521 AC: 1 AN: 1918

European-Non Finnish (NFE) AF: 0.00000316 AC: 1 AN: 316086

Other (OTH) AF: 0.00 AC: 0 AN: 25318

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000835220), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000225 AC: 2 AN: 89044 Hom.: 0 Cov.: 12 AF XY: 0.0000485 AC XY: 2 AN XY: 41252

African (AFR) AF: 0.0000913 AC: 2 AN: 21906

American (AMR) AF: 0.00 AC: 0 AN: 8382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2436

East Asian (EAS) AF: 0.00 AC: 0 AN: 2340

South Asian (SAS) AF: 0.00 AC: 0 AN: 2360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44676

Other (OTH) AF: 0.00 AC: 0 AN: 1222

Alfa AF: 0.0000843 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	Uncertain	0.42
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	4.1	H
PhyloP100		5.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.92		Loss of disorder (P = 0.0533)
MVP		0.39
MPC		3.4
ClinPred		1.0	D
GERP RS		2.5
PromoterAI		-0.037	Neutral
Varity_R		0.53
gMVP		0.54
Mutation Taster		=89/11	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: rs1344888245; hg19: chr16-69986010;