rs7290488

chr22-37185343-C-T

Variant summary

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

The NM_031910.4(C1QTNF6):c.164G>A(p.Gly55Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,613,360 control chromosomes in the GnomAD database, including 23,076 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 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. G55S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.13 (1563 hom., cov: 31)
  • Exomes 𝑓: 0.16 (21513 hom.)
• Consequence: C1QTNF6 NM_031910.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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=0.0018802285).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QTNF6	NM_031910.4	c.164G>A	p.Gly55Asp	missense_variant	2/3	ENST00000337843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QTNF6	ENST00000337843.7	c.164G>A	p.Gly55Asp	missense_variant	2/3	1	NM_031910.4	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19988 AN: 152054 Hom.: 1564 Cov.: 31

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.144

GnomAD3 exomes AF: 0.123 AC: 30808 AN: 249906 Hom.: 2350 AF XY: 0.123 AC XY: 16696 AN XY: 135264

Gnomad AFR exome AF: 0.0777

Gnomad AMR exome AF: 0.0885

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.000273

Gnomad SAS exome AF: 0.0475

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.164 AC: 239572 AN: 1461188 Hom.: 21513 Cov.: 32 AF XY: 0.161 AC XY: 116904 AN XY: 726914

Gnomad4 AFR exome AF: 0.0682

Gnomad4 AMR exome AF: 0.0928

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.000328

Gnomad4 SAS exome AF: 0.0506

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.131 AC: 19992 AN: 152172 Hom.: 1563 Cov.: 31 AF XY: 0.126 AC XY: 9361 AN XY: 74388

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0474

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.143

Alfa AF: 0.163 Hom.: 3231

Bravo AF: 0.130

TwinsUK AF: 0.201 AC: 747

ALSPAC AF: 0.198 AC: 762

ESP6500AA AF: 0.0833 AC: 367

ESP6500EA AF: 0.177 AC: 1518

ExAC AF: 0.122 AC: 14785

Asia WGS AF: 0.0330 AC: 115 AN: 3478

EpiCase AF: 0.179

EpiControl AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	3.3
Dann	Benign	0.95
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.079	N
MetaRNN	Benign	0.0019	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.44	N;N;D
REVEL	Benign	0.044
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.22	T;T;D
Vest4		0.20
MPC		0.46
ClinPred		0.0037	T
GERP RS		1.1
Varity_R		0.037
gMVP		0.46

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: rs7290488; hg19: chr22-37581383;