chr14-59525316-T-C

Variant names:

• chr14-59525316-T-C
• rs755728050
• NM_001164399.2:c.1961A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164399.2(CCDC175):​c.1961A>G​(p.Asp654Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,310,404 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D654A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CCDC175 NM_001164399.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• Publications: 0 publications found

Genes affected

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

ENSG00000258782 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12813482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC175	NM_001164399.2	c.1961A>G	p.Asp654Gly	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.1961A>G	p.Asp654Gly	missense_variant	Exon 16 of 20	5	NM_001164399.2	ENSP00000453940.1
CCDC175	ENST00000281581.5	c.1961A>G	p.Asp654Gly	missense_variant	Exon 16 of 20	5		ENSP00000452964.1
ENSG00000258782	ENST00000554253.1	n.122A>G		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.63e-7 AC: 1 AN: 1310404 Hom.: 0 Cov.: 27 AF XY: 0.00000155 AC XY: 1 AN XY: 644306

African (AFR) AF: 0.00 AC: 0 AN: 26858

American (AMR) AF: 0.00 AC: 0 AN: 18442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22328

East Asian (EAS) AF: 0.00 AC: 0 AN: 32686

South Asian (SAS) AF: 0.00 AC: 0 AN: 66762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4942

European-Non Finnish (NFE) AF: 9.52e-7 AC: 1 AN: 1050108

Other (OTH) AF: 0.00 AC: 0 AN: 54582

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;.
PhyloP100		2.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.2	N;N
Sift	Benign	0.056	T;T
Sift4G	Benign	0.084	T;T
Vest4		0.23
MVP		0.10
ClinPred		0.077	T
GERP RS		3.6
Varity_R		0.068
gMVP		0.14
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs755728050; hg19: chr14-59992034;