chr9-15571638-C-T

Position:

• chr9-15571638-C-T

Variant summary

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

The NM_173550.4(CCDC171):​c.56C>T​(p.Ser19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000711 in 1,406,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: CCDC171 NM_173550.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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=0.14539415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC171	NM_173550.4	c.56C>T	p.Ser19Leu	missense_variant	3/26	ENST00000380701.8	NP_775821.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC171	ENST00000380701.8	c.56C>T	p.Ser19Leu	missense_variant	3/26	1	NM_173550.4	ENSP00000370077	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000711 AC: 10 AN: 1406612 Hom.: 0 Cov.: 27 AF XY: 0.00000857 AC XY: 6 AN XY: 700042

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000261

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000733

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Feb 08, 2023

The c.56C>T (p.S19L) alteration is located in exon 3 (coding exon 2) of the CCDC171 gene. This alteration results from a C to T substitution at nucleotide position 56, causing the serine (S) at amino acid position 19 to be replaced by a leucine (L). 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	0.093
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.057
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.038	D
Polyphen		0.57	P
Vest4		0.44
MutPred		0.31		Loss of disorder (P = 0.0306);
MVP		0.13
ClinPred		0.36	T
GERP RS		4.6
Varity_R		0.14
gMVP		0.074

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-15571636; COSMIC: COSV105874690;