Genetic Variant C1QTNF1:p.Ser45Trp (chr17-79044102-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030968.5(C1QTNF1):c.134C>G(p.Ser45Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. S45L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

C1QTNF1
NM_030968.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.404

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17387858).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030968.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1QTNF1	NM_030968.5	MANE Select	c.134C>G	p.Ser45Trp	missense	Exon 2 of 4	NP_112230.1	Q9BXJ1-1
C1QTNF1	NM_153372.3		c.134C>G	p.Ser45Trp	missense	Exon 2 of 4	NP_699203.1	Q9BXJ1-1
C1QTNF1	NM_198593.4		c.134C>G	p.Ser45Trp	missense	Exon 2 of 4	NP_940995.1	Q9BXJ1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1QTNF1	ENST00000579760.6	TSL:1 MANE Select	c.134C>G	p.Ser45Trp	missense	Exon 2 of 4	ENSP00000463922.1	Q9BXJ1-1
C1QTNF1	ENST00000580474.1	TSL:1	c.134C>G	p.Ser45Trp	missense	Exon 1 of 3	ENSP00000463108.1	Q9BXJ1-1
C1QTNF1	ENST00000581774.5	TSL:1	c.134C>G	p.Ser45Trp	missense	Exon 2 of 4	ENSP00000462481.2	Q9BXJ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459156

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

86126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5504

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110380

Other (OTH)

AF:

0.00

AC:

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.025

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.58

M_CAP

Benign

0.037

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.69

PhyloP100

0.40

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.99

REVEL

Benign

0.26

Sift

Benign

0.092

Sift4G

Benign

0.078

Polyphen

0.93

Vest4

0.30

MutPred

0.40

Loss of glycosylation at S45 (P = 0.0037)

MVP

0.82

MPC

0.77

ClinPred

0.35

GERP RS

1.4

Varity_R

0.056

gMVP

0.40

Mutation Taster

=297/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over