22-37182616-C-T

Variant names:

• chr22-37182616-C-T
• rs986273635
• NM_031910.4:c.409G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031910.4(C1QTNF6):​c.409G>A​(p.Ala137Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: C1QTNF6 NM_031910.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.233
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039829463).

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.409G>A	p.Ala137Thr	missense	Exon 3 of 3	NP_114116.3
	C1QTNF6	NM_182486.2		c.409G>A	p.Ala137Thr	missense	Exon 3 of 4	NP_872292.1	Q9BXI9-2
	C1QTNF6	NM_001365878.1		c.352G>A	p.Ala118Thr	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.409G>A	p.Ala137Thr	missense	Exon 3 of 3	ENSP00000338812.2	Q9BXI9-2
	C1QTNF6	ENST00000397110.6	TSL:1	c.409G>A	p.Ala137Thr	missense	Exon 3 of 4	ENSP00000380299.2	Q9BXI9-2
	C1QTNF6	ENST00000493023.1	TSL:1	n.851G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 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	Benign	0.067
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.1
DANN	Benign	0.85
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.88	T
PhyloP100		0.23
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.073
Sift	Benign	0.42	T
Sift4G	Benign	0.57	T
Vest4		0.064
MVP		0.15
MPC		0.23
ClinPred		0.041	T
GERP RS		-7.6
Varity_R		0.041
gMVP		0.076
Mutation Taster		=98/2	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: rs986273635; hg19: chr22-37578656;