dbSNP rs2072628888: C1QTNF1:p.Leu174Ile (chr17-79047762-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030968.5(C1QTNF1):c.520C>A(p.Leu174Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L174V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

C1QTNF1
NM_030968.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF1	NM_030968.5 link	c.520C>A	p.Leu174Ile	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>A	p.Leu174Ile	missense_variant	Exon 4 of 4	1	NM_030968.5	ENSP00000463922.1		Q9BXJ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

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

African (AFR)

AF:

0.00

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:

0.0000166

AC:

AN:

60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

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

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.50

D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.62

MutationAssessor

Benign

1.5

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

PhyloP100

5.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.4

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

REVEL

Uncertain

0.50

Sift

Benign

0.21

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

Sift4G

Benign

0.21

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

Polyphen

0.95

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

Vest4

0.49

MutPred

0.49

.;Loss of solvent accessibility (P = 0.0404);Loss of solvent accessibility (P = 0.0404);Loss of solvent accessibility (P = 0.0404);Loss of solvent accessibility (P = 0.0404);.;Loss of solvent accessibility (P = 0.0404);Loss of solvent accessibility (P = 0.0404);Loss of solvent accessibility (P = 0.0404);Loss of solvent accessibility (P = 0.0404);

MVP

0.98

MPC

0.99

ClinPred

0.97

GERP RS

4.7

Varity_R

0.20

gMVP

0.16

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

Computational scores

Splicing

Publications

Other links and lift over