Genetic Variant C1QTNF1:p.Leu174Val (chr17-79047762-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_030968.5(C1QTNF1):c.520C>G(p.Leu174Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

C1QTNF1
NM_030968.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Publications

0 publications found

Variant links:

Genes affected

C1QTNF1 (HGNC:14324): (C1q and TNF related 1) Enables collagen binding activity. Involved in several processes, including negative regulation of platelet aggregation; positive regulation of aldosterone secretion; and positive regulation of cytosolic calcium ion concentration. Located in extracellular space. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3194965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF1	NM_030968.5 link	c.520C>G	p.Leu174Val	missense_variant	Exon 4 of 4	ENST00000579760.6	NP_112230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF1	ENST00000579760.6 link	c.520C>G	p.Leu174Val	missense_variant	Exon 4 of 4	1	NM_030968.5	ENSP00000463922.1		Q9BXJ1-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00000137

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 30, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.520C>G (p.L174V) alteration is located in exon 4 (coding exon 3) of the C1QTNF1 gene. This alteration results from a C to G substitution at nucleotide position 520, causing the leucine (L) at amino acid position 174 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

0.0022

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T;T;T;T;T;T;T;T;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

.;D;.;.;.;D;.;.;.;.

M_CAP

Benign

0.052

MetaRNN

Benign

0.32

T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.42

MutationAssessor

Benign

1.8

.;L;L;L;L;.;L;L;L;L

PhyloP100

5.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

.;.;.;.;N;N;.;.;.;.

REVEL

Uncertain

0.33

Sift

Benign

0.48

.;.;.;.;T;T;.;.;.;.

Sift4G

Benign

0.30

T;T;T;T;T;T;T;T;T;T

Polyphen

0.77

.;P;P;P;P;.;P;P;P;P

Vest4

0.26

MutPred

0.47

.;Loss of solvent accessibility (P = 0.0364);Loss of solvent accessibility (P = 0.0364);Loss of solvent accessibility (P = 0.0364);Loss of solvent accessibility (P = 0.0364);.;Loss of solvent accessibility (P = 0.0364);Loss of solvent accessibility (P = 0.0364);Loss of solvent accessibility (P = 0.0364);Loss of solvent accessibility (P = 0.0364);

MVP

0.97

MPC

0.78

ClinPred

0.87

GERP RS

4.7

Varity_R

0.34

gMVP

0.29

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over