Genetic Variant KIN:p.Arg379His (chr10-7756126-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_012311.4(KIN):c.1136G>A(p.Arg379His) variant causes a missense change. The variant allele was found at a frequency of 0.000121 in 1,585,300 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

KIN
NM_012311.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.40

Publications

1 publications found

Variant links:

Genes affected

KIN (HGNC:6327): (Kin17 DNA and RNA binding protein) The protein encoded by this gene is a nuclear protein that forms intranuclear foci during proliferation and is redistributed in the nucleoplasm during the cell cycle. Short-wave ultraviolet light provokes the relocalization of the protein, suggesting its participation in the cellular response to DNA damage. Originally selected based on protein-binding with RecA antibodies, the mouse protein presents a limited similarity with a functional domain of the bacterial RecA protein, a characteristic shared by this human ortholog. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

KIN links:

ITIH2 (HGNC:6167): (inter-alpha-trypsin inhibitor heavy chain 2) The inter-alpha-trypsin inhibitors (ITI) are a family of structurally related plasma serine protease inhibitors involved in extracellular matrix stabilization and in prevention of tumor metastasis. The ITI family contains multiple proteins made up of a light chain (see MIM 176870) and a variable number of heavy chains (Salier et al., 1987 [PubMed 2446322]; Himmelfarb et al., 2004 [PubMed 14744536]).[supplied by OMIM, Nov 2009]

ITIH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012311.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIN	NM_012311.4	MANE Select	c.1136G>A	p.Arg379His	missense	Exon 13 of 13	NP_036443.1	O60870-1
	KIN	NR_045609.2		n.1180-2057G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIN	ENST00000379562.9	TSL:1 MANE Select	c.1136G>A	p.Arg379His	missense	Exon 13 of 13	ENSP00000368881.3	O60870-1
KIN	ENST00000929809.1		c.1214G>A	p.Arg405His	missense	Exon 14 of 14	ENSP00000599868.1
KIN	ENST00000899952.1		c.1169G>A	p.Arg390His	missense	Exon 14 of 14	ENSP00000570011.1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000850

AC:

AN:

235196

AF XY:

0.0000864

show subpopulations

Gnomad AFR exome

AF:

0.0000636

Gnomad AMR exome

AF:

0.0000338

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

AF:

0.000125

AC:

179

AN:

1433226

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

712348

show subpopulations

African (AFR)

AF:

0.0000614

AC:

AN:

32548

American (AMR)

AF:

0.0000244

AC:

AN:

41048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25642

East Asian (EAS)

AF:

0.00

AC:

AN:

39126

South Asian (SAS)

AF:

0.0000749

AC:

AN:

80068

European-Finnish (FIN)

AF:

0.0000568

AC:

AN:

52836

Middle Eastern (MID)

AF:

0.000527

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.000134

AC:

147

AN:

1096834

Other (OTH)

AF:

0.000286

AC:

AN:

59432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000183

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.000107

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0078

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.8

PhyloP100

4.4

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.23

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Polyphen

0.99

Vest4

0.41

MVP

0.75

MPC

0.70

ClinPred

0.32

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.51

gMVP

0.36

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.23

Position offset: 16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over