Genetic Variant C1QTNF6:p.Pro42His (chr22-37185382-G-T) – 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_031910.4(C1QTNF6):c.125C>A(p.Pro42His) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,294 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. P42T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

C1QTNF6
NM_031910.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.87

Publications

44 publications found

Variant links:

Genes affected

C1QTNF6 (HGNC:14343): (C1q and TNF related 6) Predicted to enable identical protein binding activity. Predicted to be located in extracellular space. Predicted to be integral component of membrane. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF6 links:

IL2RB-AS1 (HGNC:40300):

IL2RB-AS1 links:

Genome browser will be placed here

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
C1QTNF6	NM_031910.4 link	c.125C>A	p.Pro42His	missense_variant	Exon 2 of 3	ENST00000337843.7	NP_114116.3	Q9BXI9-2A0A024R1J0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF6	ENST00000337843.7 link	c.125C>A	p.Pro42His	missense_variant	Exon 2 of 3	1	NM_031910.4	ENSP00000338812.2		Q9BXI9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250112

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461294

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726952

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111806

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.41

.;T;T

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.73

D;D;D

MetaSVM

Benign

-0.45

PhyloP100

4.9

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Uncertain

0.36

Sift

Benign

0.031

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Vest4

0.69

MVP

0.59

MPC

0.80

ClinPred

0.92

GERP RS

4.5

Varity_R

0.19

gMVP

0.61

Mutation Taster

=84/16

polymorphism

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over