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GeneBe

2-85053283-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_020122.5(KCMF1):c.1020T>C(p.Asp340=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,962 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 5 hom. )

Consequence

KCMF1
NM_020122.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.230
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-85053283-T-C is Benign according to our data. Variant chr2-85053283-T-C is described in ClinVar as [Benign]. Clinvar id is 787236.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.23 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00564 (858/152254) while in subpopulation AFR AF= 0.0194 (807/41548). AF 95% confidence interval is 0.0183. There are 8 homozygotes in gnomad4. There are 385 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KCMF1NM_020122.5 linkuse as main transcriptc.1020T>C p.Asp340= synonymous_variant 7/7 ENST00000409785.9
KCMF1XM_006712052.4 linkuse as main transcriptc.1044T>C p.Asp348= synonymous_variant 7/7
KCMF1XM_047445126.1 linkuse as main transcriptc.867T>C p.Asp289= synonymous_variant 8/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KCMF1ENST00000409785.9 linkuse as main transcriptc.1020T>C p.Asp340= synonymous_variant 7/71 NM_020122.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00563
AC:
856
AN:
152136
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0194
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00203
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:
0.000118
Gnomad OTH
AF:
0.00573
GnomAD3 exomes
AF:
0.00165
AC:
412
AN:
249230
Hom.:
0
AF XY:
0.00124
AC XY:
168
AN XY:
135206
show subpopulations
Gnomad AFR exome
AF:
0.0223
Gnomad AMR exome
AF:
0.00130
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000133
Gnomad OTH exome
AF:
0.000826
GnomAD4 exome
AF:
0.000647
AC:
946
AN:
1461708
Hom.:
5
Cov.:
31
AF XY:
0.000580
AC XY:
422
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.0206
Gnomad4 AMR exome
AF:
0.00154
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000711
Gnomad4 OTH exome
AF:
0.00156
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00564
AC:
858
AN:
152254
Hom.:
8
Cov.:
32
AF XY:
0.00517
AC XY:
385
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0194
Gnomad4 AMR
AF:
0.00203
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00567
Alfa
AF:
0.00163
Hom.:
0
Bravo
AF:
0.00643
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
4.4
Dann
Benign
0.57

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.

Other links and lift over

dbSNP: rs115702180; hg19: chr2-85280406; API