Variant 2-85049523-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The ENST00000409785.9(KCMF1):c.759C>T(p.Asn253=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 1,614,032 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 4 hom. )

Consequence

KCMF1
ENST00000409785.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.193

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 2-85049523-C-T is Benign according to our data. Variant chr2-85049523-C-T is described in ClinVar as [Benign]. Clinvar id is 728996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.193 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCMF1	NM_020122.5 linkuse as main transcript	c.759C>T	p.Asn253=	synonymous_variant	6/7	ENST00000409785.9	NP_064507.3
KCMF1	XM_006712052.4 linkuse as main transcript	c.783C>T	p.Asn261=	synonymous_variant	6/7		XP_006712115.1
KCMF1	XM_047445126.1 linkuse as main transcript	c.606C>T	p.Asn202=	synonymous_variant	7/8		XP_047301082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCMF1	ENST00000409785.9 linkuse as main transcript	c.759C>T	p.Asn253=	synonymous_variant	6/7	1	NM_020122.5	ENSP00000386738	P1

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

293

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00671

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000545

AC:

136

AN:

249710

Hom.:

AF XY:

0.000384

AC XY:

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.00759

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000658

GnomAD4 exome

AF:

0.000259

AC:

379

AN:

1461708

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

142

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00836

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.00192

AC:

293

AN:

152324

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00669

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00216

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.5

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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