NM_001164399.2:c.1606G>C

Variant names:

• chr14-59538040-C-G
• rs1309372798
• NM_001164399.2:c.1606G>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.1606G>C​(p.Glu536Gln) 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. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. E536K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC175 NM_001164399.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 1 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=0.12954211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC175	NM_001164399.2	c.1606G>C	p.Glu536Gln	missense_variant	Exon 13 of 20	ENST00000537690.7	NP_001157871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC175	ENST00000537690.7	c.1606G>C	p.Glu536Gln	missense_variant	Exon 13 of 20	5	NM_001164399.2	ENSP00000453940.1
CCDC175	ENST00000281581.5	c.1606G>C	p.Glu536Gln	missense_variant	Exon 13 of 20	5		ENSP00000452964.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.
PhyloP100		1.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N;N
Sift	Uncertain	0.019	D;D
Sift4G	Benign	0.081	T;T
Vest4		0.17
MVP		0.014
ClinPred		0.36	T
GERP RS		4.0
Varity_R		0.13
gMVP		0.12
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1309372798; hg19: chr14-60004758;