chr19-17936509-A-C

Position:

• chr19-17936509-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001136203.2(CCDC124):​c.89A>C​(p.Lys30Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC124 NM_001136203.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09

Genes affected

CCDC124 (HGNC:25171): (coiled-coil domain containing 124) Enables RNA binding activity. Predicted to be involved in cell division. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC124 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27981573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC124	NM_001136203.2	c.89A>C	p.Lys30Thr	missense_variant	2/5	ENST00000445755.7	NP_001129675.1
CCDC124	NM_138442.4	c.89A>C	p.Lys30Thr	missense_variant	2/5		NP_612451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC124	ENST00000445755.7	c.89A>C	p.Lys30Thr	missense_variant	2/5	2	NM_001136203.2	ENSP00000408730.1
CCDC124	ENST00000597436.5	c.89A>C	p.Lys30Thr	missense_variant	2/5	1		ENSP00000471455.1
CCDC124	ENST00000596123.1	c.89A>C	p.Lys30Thr	missense_variant	1/3	2		ENSP00000472520.1
CCDC124	ENST00000602080.1	n.126A>C		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jun 22, 2023

The c.89A>C (p.K30T) alteration is located in exon 2 (coding exon 1) of the CCDC124 gene. This alteration results from a A to C substitution at nucleotide position 89, causing the lysine (K) at amino acid position 30 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.5	D;.;.
REVEL	Benign	0.13
Sift	Benign	0.11	T;.;.
Sift4G	Benign	0.16	T;T;T
Polyphen		0.81	P;P;.
Vest4		0.34
MutPred		0.18		Gain of phosphorylation at K30 (P = 0.0143);Gain of phosphorylation at K30 (P = 0.0143);Gain of phosphorylation at K30 (P = 0.0143);
MVP		0.63
MPC		0.69
ClinPred		0.92	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.16

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: chr19-18047318;