14-57471447-C-T

Variant names:

• chr14-57471447-C-T
• rs181050215
• NM_018168.4:c.799G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018168.4(CCDC198):​c.799G>A​(p.Glu267Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,614,028 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00031 (2 hom.)
• Consequence: CCDC198 NM_018168.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013905019).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC198	NM_018168.4	c.799G>A	p.Glu267Lys	missense_variant	Exon 6 of 6	ENST00000216445.8	NP_060638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC198	ENST00000216445.8	c.799G>A	p.Glu267Lys	missense_variant	Exon 6 of 6	1	NM_018168.4	ENSP00000216445.3

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152060 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000382 AC: 96 AN: 251448 Hom.: 0 AF XY: 0.000493 AC XY: 67 AN XY: 135892

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000549

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000312 AC: 456 AN: 1461850 Hom.: 2 Cov.: 40 AF XY: 0.000363 AC XY: 264 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000537

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00154

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000242

Gnomad4 OTH exome AF: 0.000364

GnomAD4 genome AF: 0.000329 AC: 50 AN: 152178 Hom.: 0 Cov.: 31 AF XY: 0.000350 AC XY: 26 AN XY: 74384

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000426 Hom.: 0

Bravo AF: 0.000261

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000395 AC: 48

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.799G>A (p.E267K) alteration is located in exon 6 (coding exon 6) of the C14orf105 gene. This alteration results from a G to A substitution at nucleotide position 799, causing the glutamic acid (E) at amino acid position 267 to be replaced by a lysine (K). 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	0.092
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.86	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.014	T;T;T
MetaSVM	Benign	-0.58	T
PROVEAN	Uncertain	-2.8	D;N;D
REVEL	Benign	0.12
Sift	Uncertain	0.026	D;D;D
Sift4G	Benign	0.068	T;D;T
Polyphen		0.83	P;D;P
Vest4		0.19
MVP		0.63
MPC		0.21
ClinPred		0.094	T
GERP RS		5.2
Varity_R		0.22
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs181050215; hg19: chr14-57938165;