chr5-34042885-G-A

Position:

• chr5-34042885-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181435.6(C1QTNF3):​c.241C>T​(p.Pro81Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1QTNF3 NM_181435.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.38

Genes affected

C1QTNF3 (HGNC:14326): (C1q and TNF related 3) Enables identical protein binding activity. Involved in several processes, including cellular triglyceride homeostasis; negative regulation of NIK/NF-kappaB signaling; and regulation of cytokine production. Acts upstream of or within negative regulation of gluconeogenesis. Located in extracellular exosome and membrane. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF3-AMACR (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29337847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QTNF3	NM_181435.6	c.241C>T	p.Pro81Ser	missense_variant	1/6	ENST00000382065.8
C1QTNF3-AMACR	NR_037951.1	n.112-7127C>T		intron_variant, non_coding_transcript_variant
C1QTNF3	NM_030945.4	c.84+157C>T		intron_variant
C1QTNF3	NR_146599.1	n.895-7127C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QTNF3	ENST00000382065.8	c.241C>T	p.Pro81Ser	missense_variant	1/6	1	NM_181435.6	P4
C1QTNF3	ENST00000231338.7	c.84+157C>T		intron_variant		1		A1
C1QTNF3	ENST00000508434.1	n.171+157C>T		intron_variant, non_coding_transcript_variant		2

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

Dec 18, 2023

The c.241C>T (p.P81S) alteration is located in exon 1 (coding exon 1) of the C1QTNF3 gene. This alteration results from a C to T substitution at nucleotide position 241, causing the proline (P) at amino acid position 81 to be replaced by a serine (S). 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
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	-0.076	T
MutationTaster	Benign	0.95	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.090	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.026	D
Sift4G	Benign	0.49	T
Vest4		0.30
MutPred		0.35		Gain of phosphorylation at P81 (P = 0.0266);
MVP		0.86
MPC		0.38
ClinPred		0.73	D
GERP RS		5.1
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs1223216469; hg19: chr5-34042990;