22-37182576-C-A

Variant names:

• chr22-37182576-C-A
• rs755754179
• NM_031910.4:c.449G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031910.4(C1QTNF6):​c.449G>T​(p.Arg150Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R150C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C1QTNF6 NM_031910.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 1 publications found

Genes affected

C1QTNF6 (HGNC:14343): (C1q and TNF related 6) Predicted to enable identical protein binding activity. Predicted to be located in extracellular space. Predicted to be integral component of membrane. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

IL2RB-AS1 (HGNC:40300):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.861

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031910.4. 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
	C1QTNF6	NM_031910.4	MANE Select	c.449G>T	p.Arg150Leu	missense	Exon 3 of 3	NP_114116.3
	C1QTNF6	NM_182486.2		c.449G>T	p.Arg150Leu	missense	Exon 3 of 4	NP_872292.1	Q9BXI9-2
	C1QTNF6	NM_001365878.1		c.392G>T	p.Arg131Leu	missense	Exon 5 of 5	NP_001352807.1	Q9BXI9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF6	ENST00000337843.7	TSL:1 MANE Select	c.449G>T	p.Arg150Leu	missense	Exon 3 of 3	ENSP00000338812.2	Q9BXI9-2
	C1QTNF6	ENST00000397110.6	TSL:1	c.449G>T	p.Arg150Leu	missense	Exon 3 of 4	ENSP00000380299.2	Q9BXI9-2
	C1QTNF6	ENST00000493023.1	TSL:1	n.891G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250436 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461718 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727158

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

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

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.15	D
PhyloP100		7.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.23	T
Vest4		0.89
MVP		0.60
MPC		0.89
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.74
gMVP		0.76
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs755754179; hg19: chr22-37578616;