NM_018168.4:c.547C>T

Variant names:

• chr14-57480703-G-A
• rs34960436
• NM_018168.4:c.547C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_018168.4(CCDC198):​c.547C>T​(p.Gln183*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 1,613,932 control chromosomes in the GnomAD database, including 896 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.022 (45 hom., cov: 32)
  • Exomes 𝑓: 0.032 (851 hom.)
• Consequence: CCDC198 NM_018168.4 stop_gained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.79
• Publications: 12 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 14-57480703-G-A is Benign according to our data. Variant chr14-57480703-G-A is described in ClinVar as Benign. ClinVar VariationId is 252719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0222 (3379/152206) while in subpopulation NFE AF = 0.0349 (2374/67986). AF 95% confidence interval is 0.0337. There are 45 homozygotes in GnomAd4. There are 1605 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 AR gene

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.547C>T	p.Gln183*	stop_gained	Exon 5 of 6	NP_060638.2	Q9NVL8
	CCDC198	NM_001283056.2		c.544C>T	p.Gln182*	stop_gained	Exon 5 of 7	NP_001269985.1	F5GWJ3
	CCDC198	NM_001283057.2		c.544C>T	p.Gln182*	stop_gained	Exon 5 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.547C>T	p.Gln183*	stop_gained	Exon 5 of 6	ENSP00000216445.3	Q9NVL8
	CCDC198	ENST00000422976.6	TSL:1	c.544C>T	p.Gln182*	stop_gained	Exon 5 of 7	ENSP00000392368.2	F5GWJ3
	CCDC198	ENST00000534126.5	TSL:1	c.544C>T	p.Gln182*	stop_gained	Exon 5 of 6	ENSP00000434003.1	E9PSE9

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3383 AN: 152088 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.00623

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0275

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0242 AC: 6096 AN: 251384 AF XY: 0.0257

Gnomad AFR exome AF: 0.00529

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.00496

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0278

Gnomad NFE exome AF: 0.0360

Gnomad OTH exome AF: 0.0293

GnomAD4 exome AF: 0.0322 AC: 47139 AN: 1461726 Hom.: 851 Cov.: 31 AF XY: 0.0321 AC XY: 23369 AN XY: 727162

African (AFR) AF: 0.00541 AC: 181 AN: 33478

American (AMR) AF: 0.0121 AC: 543 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 128 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39688

South Asian (SAS) AF: 0.0234 AC: 2021 AN: 86250

European-Finnish (FIN) AF: 0.0295 AC: 1578 AN: 53420

Middle Eastern (MID) AF: 0.0382 AC: 220 AN: 5766

European-Non Finnish (NFE) AF: 0.0368 AC: 40870 AN: 1111884

Other (OTH) AF: 0.0264 AC: 1594 AN: 60388

GnomAD4 genome AF: 0.0222 AC: 3379 AN: 152206 Hom.: 45 Cov.: 32 AF XY: 0.0216 AC XY: 1605 AN XY: 74420

African (AFR) AF: 0.00621 AC: 258 AN: 41544

American (AMR) AF: 0.0152 AC: 232 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0224 AC: 108 AN: 4820

European-Finnish (FIN) AF: 0.0275 AC: 291 AN: 10592

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0349 AC: 2374 AN: 67986

Other (OTH) AF: 0.0241 AC: 51 AN: 2116

Alfa AF: 0.0291 Hom.: 249

Bravo AF: 0.0209

TwinsUK AF: 0.0386 AC: 143

ALSPAC AF: 0.0340 AC: 131

ESP6500AA AF: 0.00681 AC: 30

ESP6500EA AF: 0.0352 AC: 303

ExAC AF: 0.0256 AC: 3113

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.0358

EpiControl AF: 0.0373

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	35
DANN	Uncertain	1.0
Eigen	Pathogenic	0.79
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.89	D
PhyloP100		2.8
Vest4		0.14
GERP RS		4.9
Mutation Taster		=147/53	polymorphism (auto)

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: rs34960436; hg19: chr14-57947421; COSMIC: COSV107243027;