chr4-15442287-C-G

Position:

• chr4-15442287-C-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.358C>G​(p.Pro120Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C1QTNF7 NM_031911.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

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=0.2257478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QTNF7	NM_031911.5	c.358C>G	p.Pro120Ala	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.358C>G	p.Pro120Ala	missense_variant	3/3	1	NM_031911.5	ENSP00000388914	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jun 29, 2023

The c.379C>G (p.P127A) alteration is located in exon 3 (coding exon 3) of the C1QTNF7 gene. This alteration results from a C to G substitution at nucleotide position 379, causing the proline (P) at amino acid position 127 to be replaced by an alanine (A). 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	0.067
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	16
DANN	Benign	0.63
DEOGEN2	Benign	0.33	.;.;T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.58	T;T;T;.
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	1.3	.;.;L;L
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N;N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.87	T;T;T;T
Polyphen		0.0	.;.;B;B
Vest4		0.16, 0.15, 0.22
MutPred		0.47		.;.;Loss of glycosylation at K124 (P = 0.0025);Loss of glycosylation at K124 (P = 0.0025);
MVP		0.87
MPC		0.077
ClinPred		0.13	T
GERP RS		2.4
Varity_R		0.051
gMVP		0.52

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: chr4-15443911;