9-15591458-G-C

Position:

• chr9-15591458-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173550.4(CCDC171):​c.445G>C​(p.Glu149Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CCDC171 NM_173550.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21066058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC171	NM_173550.4	c.445G>C	p.Glu149Gln	missense_variant	5/26	ENST00000380701.8	NP_775821.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC171	ENST00000380701.8	c.445G>C	p.Glu149Gln	missense_variant	5/26	1	NM_173550.4	ENSP00000370077	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455806 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724288

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Aug 04, 2022

The c.445G>C (p.E149Q) alteration is located in exon 5 (coding exon 4) of the CCDC171 gene. This alteration results from a G to C substitution at nucleotide position 445, causing the glutamic acid (E) at amino acid position 149 to be replaced by a glutamine (Q). 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	Benign	0.086
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.21
Sift	Benign	0.65	T
Sift4G	Benign	0.22	T
Polyphen		0.96	D
Vest4		0.42
MutPred		0.11		Gain of MoRF binding (P = 0.0353);
MVP		0.24
ClinPred		0.74	D
GERP RS		5.6
Varity_R		0.048
gMVP		0.048

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-15591456;