1-169421916-A-T

Position:

• chr1-169421916-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001300969.2(CCDC181):​c.515T>A​(p.Phe172Tyr) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F172S) has been classified as Likely benign.

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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024499446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC181	NM_001300969.2	c.515T>A	p.Phe172Tyr	missense_variant	3/6	ENST00000367806.8	NP_001287898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC181	ENST00000367806.8	c.515T>A	p.Phe172Tyr	missense_variant	3/6	1	NM_001300969.2	ENSP00000356780.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.043
DANN	Benign	0.27
DEOGEN2	Benign	0.0018	T;.;.;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.053	T;.;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.024	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.5	N;N;N;N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.72	N;N;N;.;N
REVEL	Benign	0.039
Sift	Benign	1.0	T;T;T;.;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;B;B;B;.
Vest4		0.051
MutPred		0.28		Loss of methylation at K173 (P = 0.0303);Loss of methylation at K173 (P = 0.0303);Loss of methylation at K173 (P = 0.0303);Loss of methylation at K173 (P = 0.0303);Loss of methylation at K173 (P = 0.0303);
MVP		0.014
MPC		0.12
ClinPred		0.069	T
GERP RS		1.7
Varity_R		0.047
gMVP		0.014

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: rs3820059; hg19: chr1-169391154;