Variant 2-85027988-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000409785.9(KCMF1):c.116G>C(p.Ser39Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,146 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Consequence

KCMF1
ENST00000409785.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

KCMF1 (HGNC:20589): (potassium channel modulatory factor 1) Enables ubiquitin protein ligase activity. Predicted to be involved in synaptic signaling. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KCMF1 links:

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ACMG classification

Classification made for transcript

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
KCMF1	NM_020122.5 linkuse as main transcript	c.116G>C	p.Ser39Thr	missense_variant	2/7	ENST00000409785.9	NP_064507.3
KCMF1	XM_006712052.4 linkuse as main transcript	c.140G>C	p.Ser47Thr	missense_variant	2/7		XP_006712115.1
KCMF1	XM_047445126.1 linkuse as main transcript	c.-38G>C		5_prime_UTR_variant	3/8		XP_047301082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KCMF1	ENST00000409785.9 linkuse as main transcript	c.116G>C	p.Ser39Thr	missense_variant	2/7	1	NM_020122.5	ENSP00000386738	P1
KCMF1	ENST00000428691.5 linkuse as main transcript	c.-38G>C		5_prime_UTR_variant	2/3	2		ENSP00000409499
KCMF1	ENST00000453448.1 linkuse as main transcript	c.-38G>C		5_prime_UTR_variant	2/5	3		ENSP00000391340
KCMF1	ENST00000456682.1 linkuse as main transcript	c.-38G>C		5_prime_UTR_variant	3/3	3		ENSP00000414214

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 05, 2022

The c.116G>C (p.S39T) alteration is located in exon 2 (coding exon 2) of the KCMF1 gene. This alteration results from a G to C substitution at nucleotide position 116, causing the serine (S) at amino acid position 39 to be replaced by a threonine (T). 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

Benign

0.14

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

0.093

MutationAssessor

Benign

0.96

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.45

Sift

Benign

0.24

Sift4G

Benign

0.54

Polyphen

0.87

Vest4

0.53

MutPred

0.42

Loss of glycosylation at S39 (P = 0.0065);

MVP

0.58

MPC

0.97

ClinPred

0.89

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over