11-32611256-C-G

Position:

• chr11-32611256-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008391.4(CCDC73):​c.2906G>C​(p.Ser969Thr) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC73 NM_001008391.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.950

Genes affected

CCDC73 (HGNC:23261): (coiled-coil domain containing 73)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13146704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC73	NM_001008391.4	c.2906G>C	p.Ser969Thr	missense_variant	17/18	ENST00000335185.10	NP_001008392.2
CCDC73	XM_047427029.1	c.2906G>C	p.Ser969Thr	missense_variant	22/23		XP_047282985.1
CCDC73	XM_047427030.1	c.2906G>C	p.Ser969Thr	missense_variant	17/18		XP_047282986.1
CCDC73	XM_047427031.1	c.2648G>C	p.Ser883Thr	missense_variant	16/17		XP_047282987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC73	ENST00000335185.10	c.2906G>C	p.Ser969Thr	missense_variant	17/18	2	NM_001008391.4	ENSP00000335325.5
CCDC73	ENST00000528333.1	c.136-8236G>C		intron_variant		3		ENSP00000434365.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.2906G>C (p.S969T) alteration is located in exon 17 (coding exon 16) of the CCDC73 gene. This alteration results from a G to C substitution at nucleotide position 2906, causing the serine (S) at amino acid position 969 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.094
Sift	Benign	0.030	D
Sift4G	Uncertain	0.032	D
Polyphen		0.64	P
Vest4		0.26
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.099
MPC		0.15
ClinPred		0.73	D
GERP RS		4.6
Varity_R		0.14
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1855420218; hg19: chr11-32632802;