chr5-144474074-A-C

Position:

• chr5-144474074-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020768.4(KCTD16):​c.1247A>C​(p.His416Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H416Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD16 NM_020768.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.87

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25328818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD16	NM_020768.4	c.1247A>C	p.His416Pro	missense_variant	4/4	ENST00000512467.6
KCTD16	NM_001370486.1	c.1247A>C	p.His416Pro	missense_variant	3/3
KCTD16	NM_001370487.1	c.1247A>C	p.His416Pro	missense_variant	3/3
KCTD16	XM_005268493.3	c.1247A>C	p.His416Pro	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD16	ENST00000512467.6	c.1247A>C	p.His416Pro	missense_variant	4/4	1	NM_020768.4	P1
KCTD16	ENST00000507359.3	c.1247A>C	p.His416Pro	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.1247A>C (p.H416P) alteration is located in exon 4 (coding exon 2) of the KCTD16 gene. This alteration results from a A to C substitution at nucleotide position 1247, causing the histidine (H) at amino acid position 416 to be replaced by a proline (P). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.027	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.38	B;B
Vest4		0.62
MutPred		0.26		Gain of catalytic residue at H416 (P = 0.0089);Gain of catalytic residue at H416 (P = 0.0089);
MVP		0.33
MPC		0.43
ClinPred		0.48	T
GERP RS		6.0
Varity_R		0.20
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-143853637;