13-36297659-A-C

Position:

• chr13-36297659-A-C

Variant summary

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

The NM_001144981.3(CCDC169):​c.61T>G​(p.Leu21Val) 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. 13/21 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: CCDC169 NM_001144981.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0500

Genes affected

CCDC169 (HGNC:34361): (coiled-coil domain containing 169)

CCDC169-SOHLH2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC169	NM_001144981.3	c.61T>G	p.Leu21Val	missense_variant	1/8	ENST00000239859.8	NP_001138453.1
CCDC169-SOHLH2	NM_001198910.2	c.-119T>G		5_prime_UTR_variant	1/16		NP_001185839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC169	ENST00000239859.8	c.61T>G	p.Leu21Val	missense_variant	1/8	5	NM_001144981.3	ENSP00000239859	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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 25, 2024

The c.61T>G (p.L21V) alteration is located in exon 1 (coding exon 1) of the CCDC169 gene. This alteration results from a T to G substitution at nucleotide position 61, causing the leucine (L) at amino acid position 21 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	D;D;D;D;D;N;N;D;D
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.16
Sift	Benign	0.12	T;T
Sift4G	Benign	0.080	T;T
Polyphen		1.0	D;D
Vest4		0.23
MutPred		0.28		Gain of MoRF binding (P = 0.0822);Gain of MoRF binding (P = 0.0822);
MVP		0.18
ClinPred		0.71	D
GERP RS		-2.7
Varity_R		0.064
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.26		Position offset: 1

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: chr13-36871796;