rs229526

Positions:

• chr22-37185382-G-C
• chr22-37185382-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000337843.7(C1QTNF6):​c.125C>G​(p.Pro42Arg) variant causes a missense change. The variant allele was found at a frequency of 0.218 in 1,613,258 control chromosomes in the GnomAD database, including 39,123 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P42T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.22 (3742 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35381 hom.)
• Consequence: C1QTNF6 ENST00000337843.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027126372).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QTNF6	NM_031910.4	c.125C>G	p.Pro42Arg	missense_variant	2/3	ENST00000337843.7	NP_114116.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QTNF6	ENST00000337843.7	c.125C>G	p.Pro42Arg	missense_variant	2/3	1	NM_031910.4	ENSP00000338812	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33148 AN: 152006 Hom.: 3730 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.211

GnomAD3 exomes AF: 0.192 AC: 47993 AN: 250112 Hom.: 4988 AF XY: 0.197 AC XY: 26610 AN XY: 135312

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0975

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.207

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.218 AC: 318018 AN: 1461136 Hom.: 35381 Cov.: 36 AF XY: 0.217 AC XY: 158046 AN XY: 726876

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.0934

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.218 AC: 33181 AN: 152122 Hom.: 3742 Cov.: 32 AF XY: 0.211 AC XY: 15720 AN XY: 74362

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.209

Alfa AF: 0.216 Hom.: 1276

Bravo AF: 0.217

TwinsUK AF: 0.223 AC: 828

ALSPAC AF: 0.231 AC: 892

ESP6500AA AF: 0.265 AC: 1169

ESP6500EA AF: 0.223 AC: 1919

ExAC AF: 0.199 AC: 24096

Asia WGS AF: 0.151 AC: 524 AN: 3478

EpiCase AF: 0.227

EpiControl AF: 0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.10
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.39	.;T;T
MetaRNN	Benign	0.0027	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.41	P;P
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.20
Sift	Benign	0.14	T;T;T
Sift4G	Uncertain	0.013	D;D;D
Vest4		0.30
MPC		0.24
ClinPred		0.027	T
GERP RS		4.5
Varity_R		0.15
gMVP		0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs229526; hg19: chr22-37581422; COSMIC: COSV55396250; COSMIC: COSV55396250;