NM_080387.5:c.269C>T

Variant names:

• chr12-8519045-C-T
• rs369634533
• NM_080387.5:c.269C>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.269C>T​(p.Ala90Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A90G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLEC4D NM_080387.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• 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=0.07749042).

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.269C>T	p.Ala90Val	missense	Exon 4 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.269C>T	p.Ala90Val	missense	Exon 4 of 6	ENSP00000299665.2	Q8WXI8
	CLEC4D	ENST00000959647.1		c.278C>T	p.Ala93Val	missense	Exon 4 of 6	ENSP00000629706.1
	CLEC4D	ENST00000382064.6	TSL:3	c.269C>T	p.Ala90Val	missense	Exon 5 of 6	ENSP00000371496.2	A6NHA5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461824 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.088	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.033
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.055
Sift	Benign	0.36	T
Sift4G	Benign	0.33	T
Polyphen		0.0060	B
Vest4		0.17
MutPred		0.56		Loss of catalytic residue at A90 (P = 0.193)
MVP		0.16
MPC		0.031
ClinPred		0.091	T
GERP RS		0.47
Varity_R		0.12
gMVP		0.18
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs369634533; hg19: chr12-8671641;