1-169421916-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001300969.2(CCDC181):​c.515T>C​(p.Phe172Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 1,613,226 control chromosomes in the GnomAD database, including 364,763 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.67 (34206 hom., cov: 31)
  • Exomes 𝑓: 0.67 (330557 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1050067E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

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>C	p.Phe172Ser	missense	Exon 3 of 6	NP_001287898.1
	CCDC181	NM_001394007.1		c.515T>C	p.Phe172Ser	missense	Exon 3 of 6	NP_001380936.1
	CCDC181	NM_001300968.1		c.515T>C	p.Phe172Ser	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>C	p.Phe172Ser	missense	Exon 3 of 6	ENSP00000356780.3
	CCDC181	ENST00000367805.7	TSL:1	c.515T>C	p.Phe172Ser	missense	Exon 3 of 6	ENSP00000356779.3
	CCDC181	ENST00000545005.5	TSL:1	c.515T>C	p.Phe172Ser	missense	Exon 4 of 7	ENSP00000442297.1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101521 AN: 151924 Hom.: 34154 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.673

GnomAD2 exomes AF: 0.682 AC: 170342 AN: 249870 AF XY: 0.668

Gnomad AFR exome AF: 0.638

Gnomad AMR exome AF: 0.777

Gnomad ASJ exome AF: 0.694

Gnomad EAS exome AF: 0.929

Gnomad FIN exome AF: 0.712

Gnomad NFE exome AF: 0.657

Gnomad OTH exome AF: 0.675

GnomAD4 exome AF: 0.669 AC: 977814 AN: 1461184 Hom.: 330557 Cov.: 50 AF XY: 0.663 AC XY: 482225 AN XY: 726954

African (AFR) AF: 0.640 AC: 21396 AN: 33424

American (AMR) AF: 0.766 AC: 34171 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 18294 AN: 26126

East Asian (EAS) AF: 0.929 AC: 36867 AN: 39686

South Asian (SAS) AF: 0.515 AC: 44412 AN: 86226

European-Finnish (FIN) AF: 0.716 AC: 38177 AN: 53350

Middle Eastern (MID) AF: 0.601 AC: 3467 AN: 5764

European-Non Finnish (NFE) AF: 0.666 AC: 740151 AN: 1111618

Other (OTH) AF: 0.677 AC: 40879 AN: 60364

GnomAD4 genome AF: 0.668 AC: 101639 AN: 152042 Hom.: 34206 Cov.: 31 AF XY: 0.671 AC XY: 49894 AN XY: 74332

African (AFR) AF: 0.637 AC: 26400 AN: 41470

American (AMR) AF: 0.717 AC: 10934 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2363 AN: 3470

East Asian (EAS) AF: 0.925 AC: 4790 AN: 5176

South Asian (SAS) AF: 0.534 AC: 2572 AN: 4812

European-Finnish (FIN) AF: 0.714 AC: 7544 AN: 10568

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44804 AN: 67978

Other (OTH) AF: 0.674 AC: 1420 AN: 2108

Alfa AF: 0.662 Hom.: 121451

Bravo AF: 0.674

TwinsUK AF: 0.668 AC: 2476

ALSPAC AF: 0.661 AC: 2549

ESP6500AA AF: 0.642 AC: 2829

ESP6500EA AF: 0.646 AC: 5549

ExAC AF: 0.672 AC: 81586

Asia WGS AF: 0.697 AC: 2428 AN: 3478

EpiCase AF: 0.649

EpiControl AF: 0.651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.10
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.048	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.12
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.023
Sift	Benign	0.40	T
Sift4G	Benign	0.42	T
Polyphen		0.0010	B
Vest4		0.014
MPC		0.19
ClinPred		0.0098	T
GERP RS		1.7
Varity_R		0.035
gMVP		0.018
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV63156612;