Variant 4-15442427-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_031911.5(C1QTNF7):c.498A>G(p.Ile166Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

C1QTNF7
NM_031911.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.311

Variant links:

Genes affected

C1QTNF7 (HGNC:14342): (C1q and TNF related 7) Predicted to enable identical protein binding activity. Predicted to be located in extracellular space. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2904614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QTNF7	NM_031911.5 linkuse as main transcript	c.498A>G	p.Ile166Met	missense_variant	3/3	ENST00000444304.3	NP_114117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QTNF7	ENST00000444304.3 linkuse as main transcript	c.498A>G	p.Ile166Met	missense_variant	3/3	1	NM_031911.5	ENSP00000388914	P1	Q9BXJ2-1
C1QTNF7	ENST00000295297.4 linkuse as main transcript	c.519A>G	p.Ile173Met	missense_variant	3/3	1		ENSP00000295297		Q9BXJ2-2
C1QTNF7	ENST00000429690.5 linkuse as main transcript	c.498A>G	p.Ile166Met	missense_variant	3/3	4		ENSP00000410722	P1	Q9BXJ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

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:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.519A>G (p.I173M) alteration is located in exon 3 (coding exon 3) of the C1QTNF7 gene. This alteration results from a A to G substitution at nucleotide position 519, causing the isoleucine (I) at amino acid position 173 to be replaced by a methionine (M). 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

0.14

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

.;T;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.86

D;D;.

M_CAP

Benign

0.045

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.4

.;L;L

MutationTaster

Benign

0.95

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

1.5

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.022

D;D;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

0.046

.;B;B

Vest4

0.19

MutPred

0.50

.;Loss of catalytic residue at L171 (P = 0.0433);Loss of catalytic residue at L171 (P = 0.0433);

MVP

0.76

MPC

0.13

ClinPred

0.46

GERP RS

1.8

Varity_R

0.092

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over