11-47590339-C-A

Variant names:

• chr11-47590339-C-A
• rs1040975912
• NM_031909.3:c.472G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031909.3(C1QTNF4):​c.472G>T​(p.Ala158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. A158V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1QTNF4 NM_031909.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36
• Publications: 0 publications found

Genes affected

C1QTNF4 (HGNC:14346): (C1q and TNF related 4) Predicted to enable cytokine activity. Involved in positive regulation of cytokine production and positive regulation of signal transduction. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18566853).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031909.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF4	NM_031909.3	MANE Select	c.472G>T	p.Ala158Ser	missense	Exon 2 of 2	NP_114115.2	Q9BXJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF4	ENST00000302514.4	TSL:1 MANE Select	c.472G>T	p.Ala158Ser	missense	Exon 2 of 2	ENSP00000302274.3	Q9BXJ3
	C1QTNF4	ENST00000862513.1		c.472G>T	p.Ala158Ser	missense	Exon 3 of 3	ENSP00000532572.1
	C1QTNF4	ENST00000954826.1		c.472G>T	p.Ala158Ser	missense	Exon 2 of 2	ENSP00000624885.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1193272 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 577486

African (AFR) AF: 0.00 AC: 0 AN: 22426

American (AMR) AF: 0.00 AC: 0 AN: 9720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15684

East Asian (EAS) AF: 0.00 AC: 0 AN: 25066

South Asian (SAS) AF: 0.00 AC: 0 AN: 53992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3334

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 985958

Other (OTH) AF: 0.00 AC: 0 AN: 48154

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.046
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.15	N
PhyloP100		2.4
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.058
Sift	Uncertain	0.021	D
Sift4G	Benign	0.14	T
Polyphen		0.25	B
Vest4		0.13
MutPred		0.70		Gain of glycosylation at A158 (P = 0.0158)
MVP		0.093
ClinPred		0.91	D
GERP RS		3.5
PromoterAI		-0.16	Neutral
Varity_R		0.15
gMVP		0.19
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs1040975912; hg19: chr11-47611891;