rs1592837700

Variant names:

• chr12-88506370-C-T
• rs1592837700
• NM_000899.5:c.723G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000899.5(KITLG):​c.723G>A​(p.Gln241Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 1,602,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: KITLG NM_000899.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0230
• Publications: 0 publications found

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 Submitted by: Labcorp Genetics (formerly Invitae)
• 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: Orphanet, G2P
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• Waardenburg syndrome, IIa 2F

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 12-88506370-C-T is Benign according to our data. Variant chr12-88506370-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 710231.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.023 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000899.5. 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
	KITLG	NM_000899.5	MANE Select	c.723G>A	p.Gln241Gln	synonymous	Exon 8 of 10	NP_000890.1	P21583-1
	KITLG	NM_003994.6		c.639G>A	p.Gln213Gln	synonymous	Exon 7 of 9	NP_003985.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KITLG	ENST00000644744.1	MANE Select	c.723G>A	p.Gln241Gln	synonymous	Exon 8 of 10	ENSP00000495951.1	P21583-1
	KITLG	ENST00000347404.10	TSL:1	c.639G>A	p.Gln213Gln	synonymous	Exon 7 of 9	ENSP00000054216.5	P21583-2
	KITLG	ENST00000378535.4	TSL:1	n.666G>A		non_coding_transcript_exon	Exon 7 of 9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000690 AC: 10 AN: 1449850 Hom.: 0 Cov.: 28 AF XY: 0.00000554 AC XY: 4 AN XY: 722230

African (AFR) AF: 0.00 AC: 0 AN: 33230

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 86048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000908 AC: 10 AN: 1101162

Other (OTH) AF: 0.00 AC: 0 AN: 59962

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.5
DANN	Benign	0.49
PhyloP100		0.023

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: rs1592837700; hg19: chr12-88900147;