9-35658426-T-C

Variant names:

• chr9-35658426-T-C
• rs1385710221
• NM_174923.3:c.47T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_174923.3(CCDC107):​c.47T>C​(p.Val16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,462,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V16L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: CCDC107 NM_174923.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

CCDC107 (HGNC:28465): (coiled-coil domain containing 107) This gene encodes a membrane protein which contains a coiled-coil domain in the central region. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.19192418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC107	NM_174923.3	c.47T>C	p.Val16Ala	missense_variant	Exon 1 of 5	ENST00000426546.7	NP_777583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC107	ENST00000426546.7	c.47T>C	p.Val16Ala	missense_variant	Exon 1 of 5	1	NM_174923.3	ENSP00000414964.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000881 AC: 8 AN: 90830 AF XY: 0.0000203

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000537

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000107 AC: 14 AN: 1310286 Hom.: 0 Cov.: 31 AF XY: 0.00000310 AC XY: 2 AN XY: 644330

African (AFR) AF: 0.00 AC: 0 AN: 26792

American (AMR) AF: 0.000536 AC: 14 AN: 26124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22478

East Asian (EAS) AF: 0.00 AC: 0 AN: 29152

South Asian (SAS) AF: 0.00 AC: 0 AN: 68888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5426

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038620

Other (OTH) AF: 0.00 AC: 0 AN: 54224

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47T>C (p.V16A) alteration is located in exon 1 (coding exon 1) of the CCDC107 gene. This alteration results from a T to C substitution at nucleotide position 47, causing the valine (V) at amino acid position 16 to be replaced by an alanine (A). 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	0.19
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.043	.;.;T;T;.;.
Eigen	Benign	0.076
Eigen_PC	Benign	0.049
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.64	T;T;T;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;.;L;L;L
PhyloP100		1.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.9	N;N;N;N;N;D
REVEL	Benign	0.056
Sift	Uncertain	0.016	D;D;D;D;D;D
Sift4G	Benign	0.15	T;T;T;T;T;T
Polyphen		0.93, 0.83	.;.;.;P;P;P
Vest4		0.29
MutPred		0.27		Gain of disorder (P = 0.0553);Gain of disorder (P = 0.0553);Gain of disorder (P = 0.0553);Gain of disorder (P = 0.0553);Gain of disorder (P = 0.0553);Gain of disorder (P = 0.0553);
MVP		0.45
MPC		0.29
ClinPred		0.50	T
GERP RS		5.4
PromoterAI		0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.16
gMVP		0.38
Mutation Taster		=83/17	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: rs1385710221; hg19: chr9-35658423;