NM_031910.4:c.752G>C

Variant names:

• chr22-37182273-C-G
• rs201227055
• NM_031910.4:c.752G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031910.4(C1QTNF6):​c.752G>C​(p.Arg251Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R251C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: C1QTNF6 NM_031910.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

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.752G>C	p.Arg251Pro	missense	Exon 3 of 3	NP_114116.3
	C1QTNF6	NM_182486.2		c.752G>C	p.Arg251Pro	missense	Exon 3 of 4	NP_872292.1	Q9BXI9-2
	C1QTNF6	NM_001365878.1		c.695G>C	p.Arg232Pro	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.752G>C	p.Arg251Pro	missense	Exon 3 of 3	ENSP00000338812.2	Q9BXI9-2
	C1QTNF6	ENST00000397110.6	TSL:1	c.752G>C	p.Arg251Pro	missense	Exon 3 of 4	ENSP00000380299.2	Q9BXI9-2
	C1QTNF6	ENST00000493023.1	TSL:1	n.1194G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250770 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 Cov.: 33

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	-0.078	T
PhyloP100		4.1
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.53
Sift	Benign	0.079	T
Sift4G	Benign	0.14	T
Vest4		0.74
MVP		0.81
MPC		0.79
ClinPred		0.91	D
GERP RS		3.7
Varity_R		0.73
gMVP		0.83
Mutation Taster		=68/32	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: rs201227055; hg19: chr22-37578313;