5-144207195-C-G

Variant names:

• chr5-144207195-C-G
• rs753433220
• NM_020768.4:c.481C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020768.4(KCTD16):​c.481C>G​(p.Arg161Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R161C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD16 NM_020768.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91
• Publications: 2 publications found

Genes affected

KCTD16 (HGNC:29244): (potassium channel tetramerization domain containing 16) Predicted to be involved in protein homooligomerization. Predicted to act upstream of or within regulation of G protein-coupled receptor signaling pathway. Predicted to be located in cell projection. Predicted to be part of receptor complex. Predicted to be active in postsynaptic membrane and presynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020768.4. 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
	KCTD16	NM_020768.4	MANE Select	c.481C>G	p.Arg161Gly	missense	Exon 3 of 4	NP_065819.1	Q68DU8
	KCTD16	NM_001370486.1		c.481C>G	p.Arg161Gly	missense	Exon 2 of 3	NP_001357415.1	Q68DU8
	KCTD16	NM_001370487.1		c.481C>G	p.Arg161Gly	missense	Exon 2 of 3	NP_001357416.1	Q68DU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD16	ENST00000512467.6	TSL:1 MANE Select	c.481C>G	p.Arg161Gly	missense	Exon 3 of 4	ENSP00000424151.1	Q68DU8
	KCTD16	ENST00000507359.3	TSL:1	c.481C>G	p.Arg161Gly	missense	Exon 2 of 3	ENSP00000426548.1	Q68DU8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250762 AF XY: 0.00

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 Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.24
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.48		Gain of ubiquitination at K162 (P = 0.0442)
MVP		0.24
MPC		0.99
ClinPred		0.92	D
GERP RS		4.2
Varity_R		0.57
gMVP		0.75
Mutation Taster		=27/73	disease causing

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: rs753433220; hg19: chr5-143586758;