17-79046661-G-T

Variant names:

• chr17-79046661-G-T
• rs758961252
• NM_030968.5:c.262G>T

Variant summary

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

The NM_030968.5(C1QTNF1):​c.262G>T​(p.Ala88Ser) 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 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A88T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C1QTNF1 NM_030968.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 2 publications found

Genes affected

C1QTNF1 (HGNC:14324): (C1q and TNF related 1) Enables collagen binding activity. Involved in several processes, including negative regulation of platelet aggregation; positive regulation of aldosterone secretion; and positive regulation of cytosolic calcium ion concentration. Located in extracellular space. Is integral component of plasma membrane. [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=0.07871044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030968.5. 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
	C1QTNF1	NM_030968.5	MANE Select	c.262G>T	p.Ala88Ser	missense	Exon 3 of 4	NP_112230.1	Q9BXJ1-1
	C1QTNF1	NM_153372.3		c.262G>T	p.Ala88Ser	missense	Exon 3 of 4	NP_699203.1	Q9BXJ1-1
	C1QTNF1	NM_198593.4		c.262G>T	p.Ala88Ser	missense	Exon 3 of 4	NP_940995.1	Q9BXJ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF1	ENST00000579760.6	TSL:1 MANE Select	c.262G>T	p.Ala88Ser	missense	Exon 3 of 4	ENSP00000463922.1	Q9BXJ1-1
	C1QTNF1	ENST00000580474.1	TSL:1	c.262G>T	p.Ala88Ser	missense	Exon 2 of 3	ENSP00000463108.1	Q9BXJ1-1
	C1QTNF1	ENST00000581774.5	TSL:1	c.262G>T	p.Ala88Ser	missense	Exon 3 of 4	ENSP00000462481.2	Q9BXJ1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.1
DANN	Benign	0.78
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.32
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.14
Sift	Benign	0.35	T
Sift4G	Benign	0.70	T
Polyphen		0.12	B
Vest4		0.067
MutPred		0.29		Gain of disorder (P = 0.0339)
MVP		0.78
MPC		0.31
ClinPred		0.41	T
GERP RS		2.1
Varity_R		0.041
gMVP		0.23
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs758961252; hg19: chr17-77042743;