chr14-57471565-C-G

Variant names:

• chr14-57471565-C-G
• rs137965995
• NM_018168.4:c.681G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018168.4(CCDC198):​c.681G>C​(p.Leu227Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000928 in 1,594,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: CCDC198 NM_018168.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.612
• Publications: 1 publications found

Genes affected

CCDC198 (HGNC:20189): (coiled-coil domain containing 198)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.007365465).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018168.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC198	NM_018168.4	MANE Select	c.681G>C	p.Leu227Phe	missense	Exon 6 of 6	NP_060638.2	Q9NVL8
	CCDC198	NM_001283056.2		c.801G>C	p.Leu267Phe	missense	Exon 7 of 7	NP_001269985.1	F5GWJ3
	CCDC198	NM_001283057.2		c.678G>C	p.Leu226Phe	missense	Exon 6 of 6	NP_001269986.1	E9PSE9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC198	ENST00000216445.8	TSL:1 MANE Select	c.681G>C	p.Leu227Phe	missense	Exon 6 of 6	ENSP00000216445.3	Q9NVL8
	CCDC198	ENST00000422976.6	TSL:1	c.801G>C	p.Leu267Phe	missense	Exon 7 of 7	ENSP00000392368.2	F5GWJ3
	CCDC198	ENST00000534126.5	TSL:1	c.678G>C	p.Leu226Phe	missense	Exon 6 of 6	ENSP00000434003.1	E9PSE9

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 151902 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000156 AC: 36 AN: 230780 AF XY: 0.000161

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00332

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000281

Gnomad OTH exome AF: 0.000538

GnomAD4 exome AF: 0.0000901 AC: 130 AN: 1442266 Hom.: 0 Cov.: 28 AF XY: 0.0000962 AC XY: 69 AN XY: 716986

African (AFR) AF: 0.00 AC: 0 AN: 32746

American (AMR) AF: 0.00 AC: 0 AN: 40584

Ashkenazi Jewish (ASJ) AF: 0.00373 AC: 95 AN: 25458

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00 AC: 0 AN: 81940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.0000154 AC: 17 AN: 1103424

Other (OTH) AF: 0.000302 AC: 18 AN: 59696

GnomAD4 genome AF: 0.000118 AC: 18 AN: 151902 Hom.: 0 Cov.: 30 AF XY: 0.0000808 AC XY: 6 AN XY: 74216

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

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

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67966

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

Alfa AF: 0.000382 Hom.: 0

Bravo AF: 0.000128

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000115 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.31
DANN	Benign	0.46
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.61
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.012
Sift	Benign	0.29	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.041
MutPred		0.41		Gain of catalytic residue at Q270 (P = 0)
MVP		0.12
MPC		0.043
ClinPred		0.018	T
GERP RS		-0.31
Varity_R		0.061
gMVP		0.070
Mutation Taster		=99/1	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: rs137965995; hg19: chr14-57938283;