Genetic Variant NM_174923.3:c.491A>C (chr9-35660826-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174923.3(CCDC107):c.491A>C(p.Lys164Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 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. 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. K164R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC107
NM_174923.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.757

Publications

0 publications found

Variant links:

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]

CCDC107 links:

ARHGEF39 (HGNC:25909): (Rho guanine nucleotide exchange factor 39) Predicted to enable guanyl-nucleotide exchange factor activity. Involved in positive regulation of cell migration. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF39 links:

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ACMG classification

Classification was made for transcript

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=0.14772329).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174923.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC107	NM_174923.3	MANE Select	c.491A>C	p.Lys164Thr	missense	Exon 5 of 5	NP_777583.2	Q8WV48-1
ARHGEF39	NM_032818.3	MANE Select	c.*1161T>G		3_prime_UTR	Exon 9 of 9	NP_116207.2	Q8N4T4-1
CCDC107	NM_001195200.2		c.491A>C	p.Lys164Thr	missense	Exon 5 of 6	NP_001182129.1	Q8WV48-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC107	ENST00000426546.7	TSL:1 MANE Select	c.491A>C	p.Lys164Thr	missense	Exon 5 of 5	ENSP00000414964.2	Q8WV48-1
CCDC107	ENST00000378409.7	TSL:1	c.491A>C	p.Lys164Thr	missense	Exon 5 of 6	ENSP00000367665.3	Q8WV48-5
ARHGEF39	ENST00000378387.4	TSL:1 MANE Select	c.*1161T>G		3_prime_UTR	Exon 9 of 9	ENSP00000367638.3	Q8N4T4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251356

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.76

M_CAP

Benign

0.011

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

0.76

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.075

Sift

Benign

0.081

Sift4G

Uncertain

0.014

Polyphen

0.98

Vest4

0.32

MutPred

0.21

Loss of ubiquitination at K164 (P = 0.0014)

MVP

0.53

MPC

0.95

ClinPred

0.59

GERP RS

1.8

Varity_R

0.070

gMVP

0.085

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over