chr4-15442581-A-G

Position:

• chr4-15442581-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031911.5(C1QTNF7):​c.652A>G​(p.Ile218Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1QTNF7 NM_031911.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25122377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QTNF7	NM_031911.5	c.652A>G	p.Ile218Val	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	c.652A>G	p.Ile218Val	missense_variant	3/3	1	NM_031911.5	ENSP00000388914	P1
C1QTNF7	ENST00000295297.4	c.673A>G	p.Ile225Val	missense_variant	3/3	1		ENSP00000295297
C1QTNF7	ENST00000429690.5	c.652A>G	p.Ile218Val	missense_variant	3/3	4		ENSP00000410722	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.673A>G (p.I225V) 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 673, causing the isoleucine (I) at amino acid position 225 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	0.30
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	.;T;T
Eigen	Benign	0.022
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.21	.;N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.49	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.041	D;D;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.088	.;B;B
Vest4		0.29
MutPred		0.48		.;Loss of stability (P = 0.0648);Loss of stability (P = 0.0648);
MVP		0.70
MPC		0.16
ClinPred		0.88	D
GERP RS		6.0
Varity_R		0.12
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-15444205;