2-85059396-T-G

Variant names:

• chr2-85059396-T-G
• rs2272514
• NM_020122.5:c.*5987T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020122.5(KCMF1):​c.*5987T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,178 control chromosomes in the GnomAD database, including 1,430 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 0.11 (1430 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCMF1 NM_020122.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 3 publications found

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]

LINC01964 (HGNC:52789): (long intergenic non-protein coding RNA 1964)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCMF1	NM_020122.5	c.*5987T>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000409785.9	NP_064507.3
KCMF1	XM_006712052.4	c.*5987T>G		3_prime_UTR_variant	Exon 7 of 7		XP_006712115.1
KCMF1	XM_047445126.1	c.*5987T>G		3_prime_UTR_variant	Exon 8 of 8		XP_047301082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCMF1	ENST00000409785.9	c.*5987T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_020122.5	ENSP00000386738.3
LINC01964	ENST00000745932.1	n.368+1920A>C		intron_variant	Intron 2 of 6
LINC01964	ENST00000745933.1	n.314+1920A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17412 AN: 152060 Hom.: 1421 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.0514

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.111

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.115 AC: 17450 AN: 152178 Hom.: 1430 Cov.: 32 AF XY: 0.115 AC XY: 8594 AN XY: 74416

African (AFR) AF: 0.187 AC: 7753 AN: 41506

American (AMR) AF: 0.0849 AC: 1299 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3468

East Asian (EAS) AF: 0.344 AC: 1779 AN: 5176

South Asian (SAS) AF: 0.0520 AC: 251 AN: 4824

European-Finnish (FIN) AF: 0.104 AC: 1099 AN: 10578

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0694 AC: 4722 AN: 68012

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.0803 Hom.: 1145

Bravo AF: 0.119

Asia WGS AF: 0.172 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.57
PhyloP100		0.19
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: rs2272514; hg19: chr2-85286519;