14-59510652-G-A

Position:

• chr14-59510652-G-A

Variant summary

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

The NM_001164399.2(CCDC175):​c.2299C>T​(p.Leu767Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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 0.0000066 (0 hom., cov: 32)
• Consequence: CCDC175 NM_001164399.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.536

Genes affected

CCDC175 (HGNC:19847): (coiled-coil domain containing 175)

CCDC175 (HGNC:):

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=0.08740136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC175	NM_001164399.2	c.2299C>T	p.Leu767Phe	missense_variant	19/20	ENST00000537690.7	NP_001157871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC175	ENST00000537690.7	c.2299C>T	p.Leu767Phe	missense_variant	19/20	5	NM_001164399.2	ENSP00000453940.1
CCDC175	ENST00000281581.5	c.2299C>T	p.Leu767Phe	missense_variant	19/20	5		ENSP00000452964.1
CCDC175	ENST00000553317.1	n.62C>T		non_coding_transcript_exon_variant	1/3	3
ENSG00000258782	ENST00000554253.1	n.460C>T		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74290

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

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

Aug 12, 2024

The c.2299C>T (p.L767F) alteration is located in exon 19 (coding exon 19) of the CCDC175 gene. This alteration results from a C to T substitution at nucleotide position 2299, causing the leucine (L) at amino acid position 767 to be replaced by a phenylalanine (F). 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	0.083
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0047	T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N;N
Sift	Uncertain	0.028	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.079
MVP		0.040
ClinPred		0.12	T
GERP RS		2.2
Varity_R		0.052
gMVP		0.042

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

LitVar

Other links and lift over

dbSNP: rs1892686790; hg19: chr14-59977370;