17-79047616-C-T

Variant names:

• chr17-79047616-C-T
• rs138383380
• NM_030968.5:c.374C>T

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.374C>T​(p.Thr125Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000418 in 1,434,268 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: C1QTNF1 NM_030968.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.388
• 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=0.04456064).

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.374C>T	p.Thr125Ile	missense	Exon 4 of 4	NP_112230.1	Q9BXJ1-1
	C1QTNF1	NM_153372.3		c.374C>T	p.Thr125Ile	missense	Exon 4 of 4	NP_699203.1	Q9BXJ1-1
	C1QTNF1	NM_198593.4		c.374C>T	p.Thr125Ile	missense	Exon 4 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.374C>T	p.Thr125Ile	missense	Exon 4 of 4	ENSP00000463922.1	Q9BXJ1-1
	C1QTNF1	ENST00000580474.1	TSL:1	c.374C>T	p.Thr125Ile	missense	Exon 3 of 3	ENSP00000463108.1	Q9BXJ1-1
	C1QTNF1	ENST00000581774.5	TSL:1	c.374C>T	p.Thr125Ile	missense	Exon 4 of 4	ENSP00000462481.2	Q9BXJ1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000429 AC: 1 AN: 233116 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000938

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000418 AC: 6 AN: 1434268 Hom.: 0 Cov.: 32 AF XY: 0.00000563 AC XY: 4 AN XY: 710468

African (AFR) AF: 0.00 AC: 0 AN: 32520

American (AMR) AF: 0.00 AC: 0 AN: 41306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24246

East Asian (EAS) AF: 0.00 AC: 0 AN: 39338

South Asian (SAS) AF: 0.00 AC: 0 AN: 82888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.00000365 AC: 4 AN: 1096792

Other (OTH) AF: 0.0000339 AC: 2 AN: 59000

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	2.1
DANN	Benign	0.91
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.39
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.27
Sift	Benign	0.28	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.31		Loss of phosphorylation at T125 (P = 0.0175)
MVP		0.59
MPC		0.31
ClinPred		0.033	T
GERP RS		-5.7
Varity_R		0.036
gMVP		0.10
Mutation Taster		=97/3	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: rs138383380; hg19: chr17-77043698;