rs193920965

Positions:

• chr9-15744627-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173550.4(CCDC171):​c.2404C>T​(p.Arg802Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CCDC171 NM_173550.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.65

Genes affected

CCDC171 (HGNC:29828): (coiled-coil domain containing 171)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC171	NM_173550.4	c.2404C>T	p.Arg802Trp	missense_variant	17/26	ENST00000380701.8	NP_775821.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC171	ENST00000380701.8	c.2404C>T	p.Arg802Trp	missense_variant	17/26	1	NM_173550.4	ENSP00000370077	P1
CCDC171	ENST00000449575.6	c.124C>T	p.Arg42Trp	missense_variant	1/11	2		ENSP00000409055

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461864 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.44		Gain of ubiquitination at K803 (P = 0.0659);
MVP		0.20
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.55
gMVP		0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs193920965; hg19: chr9-15744625; COSMIC: COSV52647665;