11-78016237-A-G

Variant names:

• chr11-78016237-A-G
• rs7928656
• NM_023930.4:c.*356T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ENSG00000254829 (HGNC:41020):

NDUFC2-KCTD14 (HGNC:42956): (NDUFC2-KCTD14 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NDUFC2 (NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2, 14.5kDa) and KCTD14 (potassium channel tetramerisation domain containing 14) genes on chromosome 11. The read-through transcripts share sequence identity with the upstream gene product and one variant has a frameshifted C-terminal region derived from the downstream gene exons. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023930.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD14	NM_023930.4	MANE Select	c.*356T>C		3_prime_UTR	Exon 2 of 2	NP_076419.2
	KCTD14	NM_001282406.2		c.*356T>C		3_prime_UTR	Exon 3 of 3	NP_001269335.1
	NDUFC2-KCTD14	NM_001203260.2		c.*1034T>C		3_prime_UTR	Exon 4 of 4	NP_001190189.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD14	ENST00000353172.6	TSL:1 MANE Select	c.*356T>C		3_prime_UTR	Exon 2 of 2	ENSP00000316482.5
	ENSG00000254829	ENST00000533697.1	TSL:3	n.428A>G		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AF: 0.322 AC: 1121 AN: 3480

American (AMR) AF: 0.265 AC: 1240 AN: 4674

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 381 AN: 3424

East Asian (EAS) AF: 0.301 AC: 1686 AN: 5604

South Asian (SAS) AF: 0.156 AC: 2500 AN: 16040

European-Finnish (FIN) AF: 0.232 AC: 1409 AN: 6074

Middle Eastern (MID) AF: 0.105 AC: 57 AN: 544

European-Non Finnish (NFE) AF: 0.140 AC: 10810 AN: 77344

Other (OTH) AF: 0.167 AC: 1131 AN: 6786

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

African (AFR) AF: 0.341 AC: 14145 AN: 41492

American (AMR) AF: 0.274 AC: 4182 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3472

East Asian (EAS) AF: 0.307 AC: 1588 AN: 5168

South Asian (SAS) AF: 0.180 AC: 869 AN: 4818

European-Finnish (FIN) AF: 0.263 AC: 2787 AN: 10586

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10092 AN: 68006

Other (OTH) AF: 0.197 AC: 416 AN: 2116

Alfa AF: 0.174 Hom.: 3629

Bravo AF: 0.232

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.78
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism (auto)

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