NM_002236.5:c.28C>T

Variant names:

• chr2-10912454-C-T
• NM_002236.5:c.28C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002236.5(KCNF1):​c.28C>T​(p.Pro10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,311,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P10Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: KCNF1 NM_002236.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

Genes affected

KCNF1 (HGNC:6246): (potassium voltage-gated channel modifier subfamily F member 1) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily F. This gene is intronless and expressed in all tissues tested, including the heart, skeletal muscle, brain, kidney, and pancreas. [provided by RefSeq, Jul 2008]

ENSG00000296957 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2546819).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002236.5. 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
	KCNF1	NM_002236.5	MANE Select	c.28C>T	p.Pro10Ser	missense	Exon 1 of 1	NP_002227.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNF1	ENST00000295082.3	TSL:6 MANE Select	c.28C>T	p.Pro10Ser	missense	Exon 1 of 1	ENSP00000295082.1	Q9H3M0
	KCNF1	ENST00000961110.1		c.28C>T	p.Pro10Ser	missense	Exon 2 of 2	ENSP00000631169.1
	ENSG00000296957	ENST00000743884.1		n.53+1945G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1311050 Hom.: 0 Cov.: 29 AF XY: 0.00000314 AC XY: 2 AN XY: 637898

African (AFR) AF: 0.00 AC: 0 AN: 28736

American (AMR) AF: 0.0000426 AC: 1 AN: 23484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19536

East Asian (EAS) AF: 0.00 AC: 0 AN: 34130

South Asian (SAS) AF: 0.0000156 AC: 1 AN: 64212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3780

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1039804

Other (OTH) AF: 0.0000186 AC: 1 AN: 53898

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.66	D
MutationAssessor	Benign	1.5	L
PhyloP100		1.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.082	T
Polyphen		0.0080	B
Vest4		0.26
MutPred		0.29		Gain of phosphorylation at P10 (P = 0.0058)
MVP		0.93
MPC		1.1
ClinPred		0.28	T
GERP RS		2.8
Varity_R		0.19
gMVP		0.57
Mutation Taster		=86/14	polymorphism

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

hg19: chr2-11052580;