11-78016237-A-G

Position:

• chr11-78016237-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023930.4(KCTD14):​c.*356T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 276,114 control chromosomes in the GnomAD database, including 6,498 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4486 hom., cov: 32)
  • Exomes 𝑓: 0.16 (2012 hom.)
• Consequence: KCTD14 NM_023930.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD14	NM_023930.4	c.*356T>C		3_prime_UTR_variant	2/2	ENST00000353172.6
NDUFC2-KCTD14	NM_001203262.2	c.*1034T>C		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD14	ENST00000353172.6	c.*356T>C		3_prime_UTR_variant	2/2	1	NM_023930.4	P1
	ENST00000533697.1	n.428A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34462 AN: 152026 Hom.: 4481 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.164 AC: 20335 AN: 123970 Hom.: 2012 Cov.: 0 AF XY: 0.164 AC XY: 10630 AN XY: 64956

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.301

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.227 AC: 34511 AN: 152144 Hom.: 4486 Cov.: 32 AF XY: 0.231 AC XY: 17217 AN XY: 74384

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.197

Alfa AF: 0.166 Hom.: 2482

Bravo AF: 0.232

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.78

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: rs7928656; hg19: chr11-77727283; COSMIC: COSV62002267; COSMIC: COSV62002267;