Variant 9-114092574-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001388308.1(KIF12):c.1665C>T(p.Cys555=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,608,682 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 25 hom. )

Consequence

KIF12
NM_001388308.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.384

Variant links:

Genes affected

KIF12 (HGNC:21495): (kinesin family member 12) This gene encodes a member of the kinesin superfamily of microtubule-associated molecular motors with functions related to the microtubule cytosekelton. Members of this superfamily play important roles in intracellular transport and cell division. A similar protein in mouse functions in the beta cell antioxidant signaling cascade, acting as a scaffold for the transcription factor specificity protein 1 (Sp1). Mice that lack this gene exhibit beta cell oxidative stress resulting in hypoinsulinemic glucose intolerance. [provided by RefSeq, Jul 2016]

KIF12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 9-114092574-G-A is Benign according to our data. Variant chr9-114092574-G-A is described in ClinVar as [Benign]. Clinvar id is 2041361.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.384 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00192 (292/152246) while in subpopulation EAS AF= 0.0261 (135/5166). AF 95% confidence interval is 0.0225. There are 1 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF12	NM_001388308.1 linkuse as main transcript	c.1665C>T	p.Cys555=	synonymous_variant	17/19	ENST00000640217.2	NP_001375237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KIF12	ENST00000640217.2 linkuse as main transcript	c.1665C>T	p.Cys555=	synonymous_variant	17/19	5	NM_001388308.1	ENSP00000491702	P1
KIF12	ENST00000640553.1 linkuse as main transcript	n.1489C>T		non_coding_transcript_exon_variant	14/16	1
KIF12	ENST00000498016.1 linkuse as main transcript	c.301+655C>T		intron_variant		5		ENSP00000491090
KIF12	ENST00000639832.1 linkuse as main transcript	n.2050C>T		non_coding_transcript_exon_variant	16/18	2

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

294

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0265

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00171

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00281

AC:

662

AN:

235384

Hom.:

AF XY:

0.00271

AC XY:

349

AN XY:

128672

show subpopulations

Gnomad AFR exome

AF:

0.0000728

Gnomad AMR exome

AF:

0.000298

Gnomad ASJ exome

AF:

0.00147

Gnomad EAS exome

AF:

0.0239

Gnomad SAS exome

AF:

0.000642

Gnomad FIN exome

AF:

0.000994

Gnomad NFE exome

AF:

0.00162

Gnomad OTH exome

AF:

0.00174

GnomAD4 exome

AF:

0.00156

AC:

2267

AN:

1456436

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

1138

AN XY:

724240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000317

Gnomad4 ASJ exome

AF:

0.00154

Gnomad4 EAS exome

AF:

0.0264

Gnomad4 SAS exome

AF:

0.000585

Gnomad4 FIN exome

AF:

0.00128

Gnomad4 NFE exome

AF:

0.000766

Gnomad4 OTH exome

AF:

0.00331

GnomAD4 genome

AF:

0.00192

AC:

292

AN:

152246

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0261

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00171

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00170

Hom.:

Bravo

AF:

0.00157

Asia WGS

AF:

0.0120

AC:

AN:

3478

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 26, 2023

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.9

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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