Genetic Variant KITLG:p.Asp210Asn (chr12-88507114-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_000899.5(KITLG):c.628G>A(p.Asp210Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,458 control chromosomes in the GnomAD database, with no homozygous occurrence. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D210G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

KITLG
NM_000899.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

0 publications found

Variant links:

Genes affected

KITLG (HGNC:6343): (KIT ligand) This gene encodes the ligand of the tyrosine-kinase receptor encoded by the KIT locus. This ligand is a pleiotropic factor that acts in utero in germ cell and neural cell development, and hematopoiesis, all believed to reflect a role in cell migration. In adults, it functions pleiotropically, while mostly noted for its continued requirement in hematopoiesis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KITLG Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 69
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
hyperpigmentation with or without hypopigmentation, familial progressive
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial progressive hyper- and hypopigmentation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial progressive hyperpigmentation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Waardenburg syndrome type 2
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
Waardenburg syndrome, IIa 2F
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

KITLG links:

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ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KITLG	NM_000899.5 link	c.628G>A	p.Asp210Asn	missense_variant	Exon 7 of 10	ENST00000644744.1	NP_000890.1	P21583-1A0A024RBC0
KITLG	NM_003994.6 link	c.544G>A	p.Asp182Asn	missense_variant	Exon 6 of 9		NP_003985.2	P21583-2A0A024RBF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1 link	c.628G>A	p.Asp210Asn	missense_variant	Exon 7 of 10		NM_000899.5	ENSP00000495951.1		P21583-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460458

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726682

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000810

AC:

AN:

1110796

Other (OTH)

AF:

0.00

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;T

Eigen

Benign

-0.054

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.72

.;T;T

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.8

L;.;L

PhyloP100

1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.85

.;N;N

REVEL

Benign

0.28

Sift

Benign

0.096

.;T;T

Sift4G

Benign

0.071

.;T;T

Polyphen

0.98

D;D;D

Vest4

0.32, 0.31

MutPred

0.76

Loss of ubiquitination at K205 (P = 0.0807);.;Loss of ubiquitination at K205 (P = 0.0807);

MVP

0.74

MPC

0.24

ClinPred

0.51

GERP RS

2.8

Varity_R

0.062

gMVP

0.23

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over