chr16-1093680-C-G

Position:

• chr16-1093680-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207419.3(C1QTNF8):​c.580G>C​(p.Ala194Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,458,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: C1QTNF8 NM_207419.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QTNF8	NM_207419.3	c.580G>C	p.Ala194Pro	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.580G>C	p.Ala194Pro	missense_variant	4/5	5	NM_207419.3	ENSP00000330426.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1458800 Hom.: 0 Cov.: 33 AF XY: 0.00000827 AC XY: 6 AN XY: 725754

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.00000831 AC: 1

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

May 30, 2023

The c.580G>C (p.A194P) 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 580, causing the alanine (A) at amino acid position 194 to be replaced by a proline (P). 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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	0.87	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.6	D;.
REVEL	Uncertain	0.53
Sift	Uncertain	0.0060	D;.
Sift4G	Uncertain	0.030	D;D
Polyphen		1.0	D;.
Vest4		0.43
MutPred		0.64		Gain of disorder (P = 0.0329);.;
MVP		0.87
MPC		0.34
ClinPred		0.98	D
GERP RS		2.4
Varity_R		0.93
gMVP		0.84

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: rs770269306; hg19: chr16-1143680;