chr4-15442264-A-T

Position:

• chr4-15442264-A-T

Variant summary

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

The NM_031911.5(C1QTNF7):​c.335A>T​(p.Lys112Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1QTNF7 NM_031911.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.66

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QTNF7	NM_031911.5	c.335A>T	p.Lys112Ile	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.335A>T	p.Lys112Ile	missense_variant	3/3	1	NM_031911.5	ENSP00000388914	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 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: 0.0000252

Gnomad4 SAS exome AF: 0.00

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

Mar 22, 2023

The c.356A>T (p.K119I) alteration is located in exon 3 (coding exon 3) of the C1QTNF7 gene. This alteration results from a A to T substitution at nucleotide position 356, causing the lysine (K) at amino acid position 119 to be replaced by an isoleucine (I). 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	0.17
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	.;.;.;D;D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;D;D;D;.
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Benign	1.0	.;.;.;L;L
MutationTaster	Benign	0.93	D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.3	D;D;D;D;D
REVEL	Uncertain	0.53
Sift	Benign	0.043	D;T;D;T;T
Sift4G	Uncertain	0.040	D;T;D;T;T
Polyphen		0.92	.;.;.;P;P
Vest4		0.39, 0.37, 0.42
MutPred		0.48		.;.;Loss of ubiquitination at K112 (P = 0.0051);Loss of ubiquitination at K112 (P = 0.0051);Loss of ubiquitination at K112 (P = 0.0051);
MVP		0.93
MPC		0.16
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.67

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: chr4-15443888;