9-15571638-C-T

Variant names:

• chr9-15571638-C-T
• NM_173550.4:c.56C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14539415).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173550.4. 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
	CCDC171	NM_173550.4	MANE Select	c.56C>T	p.Ser19Leu	missense	Exon 3 of 26	NP_775821.2
	CCDC171	NM_001355547.1		c.56C>T	p.Ser19Leu	missense	Exon 2 of 25	NP_001342476.1	Q6TFL3-4
	CCDC171	NM_001348002.2		c.-386C>T		5_prime_UTR	Exon 3 of 27	NP_001334931.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC171	ENST00000380701.8	TSL:1 MANE Select	c.56C>T	p.Ser19Leu	missense	Exon 3 of 26	ENSP00000370077.3	Q6TFL3-1
	CCDC171	ENST00000905141.1		c.56C>T	p.Ser19Leu	missense	Exon 3 of 26	ENSP00000575200.1
	CCDC171	ENST00000971281.1		c.56C>T	p.Ser19Leu	missense	Exon 3 of 26	ENSP00000641340.1

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

⚠️ 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: 29766

American (AMR) AF: 0.00 AC: 0 AN: 30140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24738

East Asian (EAS) AF: 0.00 AC: 0 AN: 37154

South Asian (SAS) AF: 0.0000261 AC: 2 AN: 76666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5618

European-Non Finnish (NFE) AF: 0.00000733 AC: 8 AN: 1091432

Other (OTH) AF: 0.00 AC: 0 AN: 58058

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000190134), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

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	0.093
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
PhyloP100		2.0
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
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

hg19: chr9-15571636; COSMIC: COSV105874690;