13-24316163-G-A

Variant names:

• chr13-24316163-G-A
• rs766110595
• NM_178540.5:c.160G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_178540.5(C1QTNF9):​c.160G>A​(p.Asp54Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000294 in 1,598,960 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000028 (1 hom.)
• Consequence: C1QTNF9 NM_178540.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• Publications: 0 publications found

Genes affected

C1QTNF9 (HGNC:28732): (C1q and TNF related 9) Enables identical protein binding activity. Predicted to be involved in signal transduction. Predicted to be located in extracellular region. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000273167 (HGNC:):

C1QTNF9-AS1 (HGNC:39906): (C1QTNF9 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22762394).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178540.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF9	NM_178540.5	MANE Select	c.160G>A	p.Asp54Asn	missense	Exon 2 of 4	NP_848635.2	P0C862
	C1QTNF9	NM_001303137.2		c.160G>A	p.Asp54Asn	missense	Exon 3 of 5	NP_001290066.1	P0C862
	C1QTNF9	NM_001303138.2		c.160G>A	p.Asp54Asn	missense	Exon 2 of 4	NP_001290067.1	P0C862

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF9	ENST00000332018.5	TSL:1 MANE Select	c.160G>A	p.Asp54Asn	missense	Exon 2 of 4	ENSP00000333737.4	P0C862
	ENSG00000273167	ENST00000382141.4	TSL:5	n.*156G>A		non_coding_transcript_exon	Exon 14 of 16	ENSP00000371576.4	A0A0A0MRY4
	ENSG00000273167	ENST00000382141.4	TSL:5	n.*156G>A		3_prime_UTR	Exon 14 of 16	ENSP00000371576.4	A0A0A0MRY4

Frequencies

GnomAD3 genomes AF: 0.0000398 AC: 6 AN: 150912 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000453 AC: 11 AN: 242892 AF XY: 0.0000305

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000283 AC: 41 AN: 1447930 Hom.: 1 Cov.: 32 AF XY: 0.0000376 AC XY: 27 AN XY: 718978

African (AFR) AF: 0.000151 AC: 5 AN: 33100

American (AMR) AF: 0.0000227 AC: 1 AN: 44120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25420

East Asian (EAS) AF: 0.00 AC: 0 AN: 39526

South Asian (SAS) AF: 0.000341 AC: 29 AN: 85026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00000363 AC: 4 AN: 1102266

Other (OTH) AF: 0.0000335 AC: 2 AN: 59788

GnomAD4 genome AF: 0.0000397 AC: 6 AN: 151030 Hom.: 0 Cov.: 30 AF XY: 0.0000543 AC XY: 4 AN XY: 73714

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000122 AC: 5 AN: 41098

American (AMR) AF: 0.0000662 AC: 1 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67754

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000161487), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.4	L
PhyloP100		3.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.41
Sift	Benign	0.18	T
Sift4G	Benign	0.26	T
Polyphen		0.51	P
Vest4		0.26
MutPred		0.36		Gain of catalytic residue at K52 (P = 0.003)
MVP		0.88
ClinPred		0.068	T
GERP RS		3.9
Varity_R		0.21
gMVP		0.18
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs766110595; hg19: chr13-24890301;