1-169421916-A-C

Variant names:

• chr1-169421916-A-C
• rs3820059
• NM_001300969.2:c.515T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001300969.2(CCDC181):​c.515T>G​(p.Phe172Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCDC181 NM_001300969.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 31 publications found

Genes affected

CCDC181 (HGNC:28051): (coiled-coil domain containing 181) Predicted to enable microtubule binding activity. Predicted to be located in manchette and sperm flagellum. [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=0.039684325).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300969.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC181	NM_001300969.2	MANE Select	c.515T>G	p.Phe172Cys	missense	Exon 3 of 6	NP_001287898.1
	CCDC181	NM_001394007.1		c.515T>G	p.Phe172Cys	missense	Exon 3 of 6	NP_001380936.1
	CCDC181	NM_001300968.1		c.515T>G	p.Phe172Cys	missense	Exon 4 of 7	NP_001287897.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC181	ENST00000367806.8	TSL:1 MANE Select	c.515T>G	p.Phe172Cys	missense	Exon 3 of 6	ENSP00000356780.3
	CCDC181	ENST00000367805.7	TSL:1	c.515T>G	p.Phe172Cys	missense	Exon 3 of 6	ENSP00000356779.3
	CCDC181	ENST00000545005.5	TSL:1	c.515T>G	p.Phe172Cys	missense	Exon 4 of 7	ENSP00000442297.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.8
DANN	Benign	0.14
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.095	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.12
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.023
Sift	Benign	0.18	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.067
MutPred		0.25		Gain of helix (P = 0.0325)
MVP		0.030
MPC		0.16
ClinPred		0.040	T
GERP RS		1.7
Varity_R		0.046
gMVP		0.018
Mutation Taster		=98/2	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: rs3820059; hg19: chr1-169391154;