NM_080387.5:c.170A>T

Variant names:

• chr12-8518212-A-T
• rs199672302
• NM_080387.5:c.170A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080387.5(CLEC4D):​c.170A>T​(p.Lys57Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,300,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K57R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CLEC4D NM_080387.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 0 publications found

Genes affected

CLEC4D (HGNC:14554): (C-type lectin domain family 4 member D) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

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=0.16163221).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080387.5. 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
	CLEC4D	NM_080387.5	MANE Select	c.170A>T	p.Lys57Met	missense	Exon 3 of 6	NP_525126.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4D	ENST00000299665.3	TSL:1 MANE Select	c.170A>T	p.Lys57Met	missense	Exon 3 of 6	ENSP00000299665.2	Q8WXI8
	CLEC4D	ENST00000959647.1		c.170A>T	p.Lys57Met	missense	Exon 3 of 6	ENSP00000629706.1
	CLEC4D	ENST00000382064.6	TSL:3	c.170A>T	p.Lys57Met	missense	Exon 4 of 6	ENSP00000371496.2	A6NHA5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1300486 Hom.: 0 Cov.: 21 AF XY: 0.00000305 AC XY: 2 AN XY: 654890

African (AFR) AF: 0.00 AC: 0 AN: 30490

American (AMR) AF: 0.00 AC: 0 AN: 44444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25116

East Asian (EAS) AF: 0.00 AC: 0 AN: 38954

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5474

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 965006

Other (OTH) AF: 0.00 AC: 0 AN: 55026

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.24
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.060
Sift	Benign	0.041	D
Sift4G	Uncertain	0.040	D
Polyphen		0.98	D
Vest4		0.32
MutPred		0.45		Loss of solvent accessibility (P = 0.0045)
MVP		0.33
MPC		0.045
ClinPred		0.46	T
GERP RS		0.63
Varity_R		0.10
gMVP		0.47
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs199672302; hg19: chr12-8670808;