chr22-37182429-C-T

Position:

• chr22-37182429-C-T

Variant summary

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

The NM_031910.4(C1QTNF6):​c.596G>A​(p.Ser199Asn) 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: 34)
• Consequence: C1QTNF6 NM_031910.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

Genes affected

C1QTNF6 (HGNC:14343): (C1q and TNF related 6) Predicted to enable identical protein binding activity. Predicted to be located in extracellular space. Predicted to be integral component of membrane. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

(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=0.39265186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QTNF6	NM_031910.4	c.596G>A	p.Ser199Asn	missense_variant	3/3	ENST00000337843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QTNF6	ENST00000337843.7	c.596G>A	p.Ser199Asn	missense_variant	3/3	1	NM_031910.4	P1
	ENST00000419128.1	n.209C>T		splice_region_variant, non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

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 14, 2023

The c.596G>A (p.S199N) alteration is located in exon 3 (coding exon 3) of the C1QTNF6 gene. This alteration results from a G to A substitution at nucleotide position 596, causing the serine (S) at amino acid position 199 to be replaced by an asparagine (N). 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	Pathogenic	0.87
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.87	T
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.17
Sift	Benign	0.082	T;T
Sift4G	Uncertain	0.025	D;D
Vest4		0.27
MVP		0.39
MPC		0.68
ClinPred		0.84	D
GERP RS		3.9
Varity_R		0.31
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr22-37578469;