chr14-59531787-T-G

Position:

• chr14-59531787-T-G

Variant summary

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

The NM_001164399.2(CCDC175):​c.1747A>C​(p.Ser583Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000595 in 1,344,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: CCDC175 NM_001164399.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.94

Genes affected

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

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=0.06475833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC175	NM_001164399.2	c.1747A>C	p.Ser583Arg	missense_variant	14/20	ENST00000537690.7	NP_001157871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC175	ENST00000537690.7	c.1747A>C	p.Ser583Arg	missense_variant	14/20	5	NM_001164399.2	ENSP00000453940.1
CCDC175	ENST00000281581.5	c.1747A>C	p.Ser583Arg	missense_variant	14/20	5		ENSP00000452964.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000159 AC: 2 AN: 125748 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000365

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000595 AC: 8 AN: 1344736 Hom.: 0 Cov.: 26 AF XY: 0.00000301 AC XY: 2 AN XY: 664320

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000569

Gnomad4 OTH exome AF: 0.0000354

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000508 Hom.: 0

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

Sep 29, 2023

The c.1747A>C (p.S583R) alteration is located in exon 14 (coding exon 14) of the CCDC175 gene. This alteration results from a A to C substitution at nucleotide position 1747, causing the serine (S) at amino acid position 583 to be replaced by an arginine (R). 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	0.25
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.0070
DANN	Benign	0.46
DEOGEN2	Benign	0.0046	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.065	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.79	N;N
Sift	Benign	0.61	T;T
Sift4G	Benign	0.58	T;T
Vest4		0.10
MVP		0.014
ClinPred		0.054	T
GERP RS		-7.0
Varity_R		0.14
gMVP		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1310565217; hg19: chr14-59998505;