chr12-48914501-A-C

Position:

• chr12-48914501-A-C

Variant summary

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

The NM_033124.5(CCDC65):​c.398A>C​(p.His133Pro) 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. 13/20 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. H133R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC65 NM_033124.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33

Genes affected

CCDC65 (HGNC:29937): (coiled-coil domain containing 65) This gene encodes a sperm tail protein that is highly expressed in adult testis, spermatocytes and spermatids. The protein plays a critical role in the assembly of the nexin-dynein regulatory complex. Mutations in this gene result in primary ciliary dyskinesia. [provided by RefSeq, Nov 2013]

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=0.060627013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC65	NM_033124.5	c.398A>C	p.His133Pro	missense_variant	3/8	ENST00000320516.5
CCDC65	NM_001286957.2	c.-32A>C		5_prime_UTR_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC65	ENST00000320516.5	c.398A>C	p.His133Pro	missense_variant	3/8	1	NM_033124.5	P2
CCDC65	ENST00000266984.9	c.398A>C	p.His133Pro	missense_variant	3/9	5		A2
CCDC65	ENST00000552942.5	c.301-3774A>C		intron_variant		5
CCDC65	ENST00000547861.5	c.*229A>C		3_prime_UTR_variant, NMD_transcript_variant	3/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.58
DEOGEN2	Benign	0.0049	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.36	N;N
REVEL	Benign	0.12
Sift	Benign	0.25	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0	.;B
Vest4		0.25
MutPred		0.39		Gain of catalytic residue at L137 (P = 0.0016);Gain of catalytic residue at L137 (P = 0.0016);
MVP		0.014
MPC		0.071
ClinPred		0.11	T
GERP RS		0.87
Varity_R		0.11
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-49308284;