11-78016690-T-G

Position:

• chr11-78016690-T-G

Variant summary

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

The NM_023930.4(KCTD14):​c.671A>C​(p.Gln224Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KCTD14 NM_023930.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.476

Genes affected

KCTD14 (HGNC:23295): (potassium channel tetramerization domain containing 14) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

NDUFC2-KCTD14 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD14	NM_023930.4	c.671A>C	p.Gln224Pro	missense_variant	2/2	ENST00000353172.6	NP_076419.2
NDUFC2-KCTD14	NM_001203262.2	c.*581A>C		3_prime_UTR_variant	3/3		NP_001190191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD14	ENST00000353172.6	c.671A>C	p.Gln224Pro	missense_variant	2/2	1	NM_023930.4	ENSP00000316482	P1
KCTD14	ENST00000533144.1	c.581A>C	p.Gln194Pro	missense_variant	3/3	1		ENSP00000431155

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Oct 29, 2021

The c.671A>C (p.Q224P) alteration is located in exon 2 (coding exon 2) of the KCTD14 gene. This alteration results from a A to C substitution at nucleotide position 671, causing the glutamine (Q) at amino acid position 224 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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.62	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.99	D;.
Vest4		0.52
MutPred		0.39		Gain of sheet (P = 0.039);.;
MVP		0.81
MPC		0.72
ClinPred		0.95	D
GERP RS		3.4
Varity_R		0.27
gMVP		0.79

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: rs779444111; hg19: chr11-77727736;