14-59531887-T-G

Variant names:

• chr14-59531887-T-G
• rs533148415
• NM_001164399.2:c.1647A>C

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.1647A>C​(p.Gln549His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,084,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CCDC175 NM_001164399.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• 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=0.12074244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC175	NM_001164399.2	c.1647A>C	p.Gln549His	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.1647A>C	p.Gln549His	missense_variant	Exon 14 of 20	5	NM_001164399.2	ENSP00000453940.1
CCDC175	ENST00000281581.5	c.1647A>C	p.Gln549His	missense_variant	Exon 14 of 20	5		ENSP00000452964.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1084252 Hom.: 0 Cov.: 17 AF XY: 0.00000183 AC XY: 1 AN XY: 546218

African (AFR) AF: 0.00 AC: 0 AN: 24712

American (AMR) AF: 0.0000692 AC: 2 AN: 28922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22656

East Asian (EAS) AF: 0.00 AC: 0 AN: 34190

South Asian (SAS) AF: 0.00 AC: 0 AN: 68000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4808

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 818752

Other (OTH) AF: 0.00 AC: 0 AN: 47538

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PhyloP100		1.9
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	D;N
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.051	T;T
Vest4		0.16
MVP		0.030
ClinPred		0.61	D
GERP RS		3.8
Varity_R		0.11
gMVP		0.059
Mutation Taster		=95/5	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: rs533148415; hg19: chr14-59998605;