rs229527

Positions:

• chr22-37185445-C-A
• chr22-37185445-C-G

Variant summary

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

The NM_031910.4(C1QTNF6):​c.62G>T​(p.Gly21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,599,432 control chromosomes in the GnomAD database, including 147,086 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 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.

• Frequency:
  • Genomes: 𝑓 0.41 (12907 hom., cov: 32)
  • Exomes 𝑓: 0.43 (134179 hom.)
• Consequence: C1QTNF6 NM_031910.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792

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=6.8937634E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QTNF6	NM_031910.4	c.62G>T	p.Gly21Val	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.62G>T	p.Gly21Val	missense_variant	2/3	1	NM_031910.4	ENSP00000338812	P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61739 AN: 151776 Hom.: 12908 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.434

GnomAD3 exomes AF: 0.432 AC: 103902 AN: 240514 Hom.: 23143 AF XY: 0.437 AC XY: 56962 AN XY: 130356

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.369

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.661

Gnomad SAS exome AF: 0.452

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.428 AC: 619783 AN: 1447538 Hom.: 134179 Cov.: 43 AF XY: 0.430 AC XY: 308798 AN XY: 718952

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.487

Gnomad4 EAS exome AF: 0.662

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.442

GnomAD4 genome AF: 0.407 AC: 61758 AN: 151894 Hom.: 12907 Cov.: 32 AF XY: 0.408 AC XY: 30256 AN XY: 74228

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.432

Alfa AF: 0.425 Hom.: 25504

Bravo AF: 0.408

TwinsUK AF: 0.428 AC: 1587

ALSPAC AF: 0.422 AC: 1626

ESP6500AA AF: 0.344 AC: 1517

ESP6500EA AF: 0.423 AC: 3638

ExAC AF: 0.431 AC: 52364

Asia WGS AF: 0.521 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.49	.;T;T
MetaRNN	Benign	0.0000069	T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.012	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N;D
REVEL	Benign	0.057
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.29	T;T;T
Vest4		0.14
MPC		0.71
ClinPred		0.016	T
GERP RS		1.0
Varity_R		0.024
gMVP		0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs229527; hg19: chr22-37581485;