chr16-1093934-C-G

Position:

• chr16-1093934-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_207419.3(C1QTNF8):​c.326G>C​(p.Gly109Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000445 in 1,347,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: C1QTNF8 NM_207419.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

Genes affected

C1QTNF8 (HGNC:31374): (C1q and TNF related 8) Involved in positive regulation of cell motility. Predicted to be located in extracellular region. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF8 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QTNF8	NM_207419.3	c.326G>C	p.Gly109Ala	missense_variant	4/5	ENST00000328449.6	NP_997302.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QTNF8	ENST00000328449.6	c.326G>C	p.Gly109Ala	missense_variant	4/5	5	NM_207419.3	ENSP00000330426.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000445 AC: 6 AN: 1347910 Hom.: 0 Cov.: 33 AF XY: 0.00000753 AC XY: 5 AN XY: 663998

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000822

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.326G>C (p.G109A) alteration is located in exon 4 (coding exon 2) of the C1QTNF8 gene. This alteration results from a G to C substitution at nucleotide position 326, causing the glycine (G) at amino acid position 109 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.77	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.62	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	0.51	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.60		Gain of stability (P = 0.0356);
MVP		0.98
MPC		0.84
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.44
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-1143934;