chr14-59525403-C-T

Variant names:

• chr14-59525403-C-T
• rs199964220
• NM_001164399.2:c.1874G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001164399.2(CCDC175):​c.1874G>A​(p.Arg625Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,513,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: CCDC175 NM_001164399.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88
• Publications: 0 publications found

Genes affected

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

ENSG00000258782 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042791843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC175	NM_001164399.2	c.1874G>A	p.Arg625Gln	missense_variant	Exon 16 of 20	ENST00000537690.7	NP_001157871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC175	ENST00000537690.7	c.1874G>A	p.Arg625Gln	missense_variant	Exon 16 of 20	5	NM_001164399.2	ENSP00000453940.1
CCDC175	ENST00000281581.5	c.1874G>A	p.Arg625Gln	missense_variant	Exon 16 of 20	5		ENSP00000452964.1
ENSG00000258782	ENST00000554253.1	n.35G>A		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 152002 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000492 AC: 6 AN: 122044 AF XY: 0.00

Gnomad AFR exome AF: 0.000145

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000452

Gnomad NFE exome AF: 0.0000374

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000264 AC: 36 AN: 1361416 Hom.: 0 Cov.: 29 AF XY: 0.0000238 AC XY: 16 AN XY: 671748

African (AFR) AF: 0.0000338 AC: 1 AN: 29582

American (AMR) AF: 0.00 AC: 0 AN: 27838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24476

East Asian (EAS) AF: 0.00 AC: 0 AN: 35200

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74590

European-Finnish (FIN) AF: 0.000115 AC: 4 AN: 34756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5618

European-Non Finnish (NFE) AF: 0.0000270 AC: 29 AN: 1072408

Other (OTH) AF: 0.0000176 AC: 1 AN: 56948

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 152002 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74222

African (AFR) AF: 0.0000242 AC: 1 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68010

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.0000782 Hom.: 0

Bravo AF: 0.0000453

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000314 AC: 1

ExAC AF: 0.000182 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1874G>A (p.R625Q) alteration is located in exon 16 (coding exon 16) of the CCDC175 gene. This alteration results from a G to A substitution at nucleotide position 1874, causing the arginine (R) at amino acid position 625 to be replaced by a glutamine (Q). 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	-0.38	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.
PhyloP100		1.9
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.0	N;N
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.16	T;T
Vest4		0.49
MVP		0.030
ClinPred		0.20	T
GERP RS		4.1
Varity_R		0.26
gMVP		0.13
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs199964220; hg19: chr14-59992121;