NM_030968.5:c.262G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030968.5(C1QTNF1):​c.262G>C​(p.Ala88Pro) 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. 17/22 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: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040846735).

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>C	p.Ala88Pro	missense	Exon 3 of 4	NP_112230.1	Q9BXJ1-1
	C1QTNF1	NM_153372.3		c.262G>C	p.Ala88Pro	missense	Exon 3 of 4	NP_699203.1	Q9BXJ1-1
	C1QTNF1	NM_198593.4		c.262G>C	p.Ala88Pro	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>C	p.Ala88Pro	missense	Exon 3 of 4	ENSP00000463922.1	Q9BXJ1-1
	C1QTNF1	ENST00000580474.1	TSL:1	c.262G>C	p.Ala88Pro	missense	Exon 2 of 3	ENSP00000463108.1	Q9BXJ1-1
	C1QTNF1	ENST00000581774.5	TSL:1	c.262G>C	p.Ala88Pro	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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.8
DANN	Benign	0.080
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	-1.5	N
PhyloP100		0.32
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.077
MutPred		0.42		Gain of disorder (P = 0.0242)
MVP		0.72
MPC		0.36
ClinPred		0.035	T
GERP RS		2.1
Varity_R		0.054
gMVP		0.33
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;