14-59531787-T-C

Variant names:

• chr14-59531787-T-C
• rs1310565217
• NM_001164399.2:c.1747A>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.1747A>G​(p.Ser583Gly) 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. 15/21 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. S583R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC175 NM_001164399.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 0 publications found

Genes affected

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

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=0.075776875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC175	NM_001164399.2	c.1747A>G	p.Ser583Gly	missense_variant	Exon 14 of 20	ENST00000537690.7	NP_001157871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC175	ENST00000537690.7	c.1747A>G	p.Ser583Gly	missense_variant	Exon 14 of 20	5	NM_001164399.2	ENSP00000453940.1
CCDC175	ENST00000281581.5	c.1747A>G	p.Ser583Gly	missense_variant	Exon 14 of 20	5		ENSP00000452964.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1344736 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 664320

African (AFR) AF: 0.00 AC: 0 AN: 29910

American (AMR) AF: 0.00 AC: 0 AN: 29614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24452

East Asian (EAS) AF: 0.00 AC: 0 AN: 35190

South Asian (SAS) AF: 0.00 AC: 0 AN: 73598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1055016

Other (OTH) AF: 0.00 AC: 0 AN: 56562

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0080
DANN	Benign	0.52
DEOGEN2	Benign	0.0068	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.
PhyloP100		-2.9
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N;N
Sift	Benign	0.47	T;T
Sift4G	Benign	0.44	T;T
Vest4		0.11
MVP		0.014
ClinPred		0.092	T
GERP RS		-7.0
Varity_R		0.081
gMVP		0.026
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1310565217; hg19: chr14-59998505;