19-18637135-C-T

Variant names:

• chr19-18637135-C-T
• rs1039574984
• NM_018316.3:c.81C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018316.3(KLHL26):​c.81C>T​(p.Asn27Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,340,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: KLHL26 NM_018316.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.9050
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373
• Publications: 0 publications found

Genes affected

KLHL26 (HGNC:25623): (kelch like family member 26)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=0.373 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL26	NM_018316.3	c.81C>T	p.Asn27Asn	splice_region_variant, synonymous_variant	Exon 1 of 3	ENST00000300976.9	NP_060786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL26	ENST00000300976.9	c.81C>T	p.Asn27Asn	splice_region_variant, synonymous_variant	Exon 1 of 3	1	NM_018316.3	ENSP00000300976.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000168 AC: 2 AN: 1187900 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 573260

African (AFR) AF: 0.0000847 AC: 2 AN: 23616

American (AMR) AF: 0.00 AC: 0 AN: 9738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16588

East Asian (EAS) AF: 0.00 AC: 0 AN: 27026

South Asian (SAS) AF: 0.00 AC: 0 AN: 45744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4568

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 978878

Other (OTH) AF: 0.00 AC: 0 AN: 48526

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74370

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.97
PhyloP100		0.37
PromoterAI		0.12	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.90
dbscSNV1_RF	Benign	0.65
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: rs1039574984; hg19: chr19-18747945;